wikidoc - User contributions [en]

C3 glomerulopathy

2017-03-09T21:51:41Z

Ali Poyan Mehr:

__NOTOC__
{{C3 glomerulopathy}}
{{CMG}} {{APM}}

{{SK}} glomerulonephritis; C3 glomerulonephritis; dense deposit disease

==[[C3 glomerulopathy overview|Overview]]==
C3 glomerulopathy is a disorder of complement system, and can be due to inherited or acquired complement dysregulation and activation of the "alternative pathway". The category of C3 glomerulopathy contains a diverse group of disorders, including those leading to the inflammatory forms of C3 glomerulopathy, namely C3 glomerulonephritis (C3GN), as wells as those presenting as dense deposit disease (DDD). Both, C3GN and DDD are marked by C3 deposition along the capillary loop, the basement membrane, and the mesangium. It is a requirement for the diagnosis of C3 glomerulopathy, that the presence of C3 deposits comes without any concomitant immunoglobulin deposition.

The activation of the alternative pathway of the complement system can be either due to inherited, or acquired defects of the complement system. The inherited forms of complement dysregulation are due to numerous identified (and potentially yet to be identified) mutations of genes involved in complement pathway (see causes). The acquired forms of complement dysregulation are mostly due to autoimmunity against complement regulatory proteins.

==[[C3 glomerulopathy historical perspective|Historical Perspective]]==
In 1915 William C. Gunn reported on the finding of low circulating complement levels in patients with acute infection and nephritic presentation (DOI: 10.1002/path.1700190202). Later on, additional reports on the involvement of complement system in other forms of inflammatory glomerulonephritis were presented, and their role further established (PMID:13568372) (PMID: 14201535) <ref name="pmid14461382">{{cite journal| author=LACHMANN PJ, MULLER-EBERHARD HJ, KUNKEL HG, PARONETTO F| title=The localization of in vivo bound complement in tissue section. | journal=J Exp Med | year= 1962 | volume= 115 | issue= | pages= 63-82 | pmid=14461382 | doi= | pmc=2137475 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14461382 }} </ref>. In the year 1962, two renowned Nephro-pathologists, Jean Berger and Pierre Galle identified a rare glomerular lesion characterized by dense intramembranous deposits on transmission EM <ref name="pmid13867660">{{cite journal| author=BERGER J, GALLE P| title=[Unusual change of the basal membranes of the kidney]. | journal=J Urol Nephrol (Paris) | year= 1962 | volume= 68 | issue= | pages= 116-22 | pmid=13867660 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13867660 }} </ref>. The term Dense Deposit Disease (DDD) was coined and described to be a disease entity associated with under belonging to the category of membrano-proliferative type glomerulonephritides (MPGN) (Mathew TH, Kincaid-Smith P). It took almost 50 years, until C3 glomerulopathy was identified as an independent disease entity, leading to potentially new diagnostic, therapeutic and prognostic opportunities <ref name="pmid170185612">{{cite journal| author=Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B et al.| title=Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. | journal=J Med Genet | year= 2007 | volume= 44 | issue= 3 | pages= 193-9 | pmid=17018561 | doi=10.1136/jmg.2006.045328 | pmc=2598029 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17018561 }}</ref> (PMID: 20606628).

==[[C3 glomerulopathy classification|Classification]]==
Until recently, C3 glomerulopathy (C3 glomerulonephritis and DDD) were categorized under as a variant of MPGN, namely MPGN type 2 (PMID: 15800116). In 2007, Servais A. et al described C3GN as an entity by itself. C3 glomerulonephritis was described as glomerular disease with deposits made up of only C3 without the presence of any immunoglobulins, that may or may not have a membranoproliferative pattern <ref name="pmid17018561">{{cite journal| author=Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B et al.| title=Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. | journal=J Med Genet | year= 2007 | volume= 44 | issue= 3 | pages= 193-9 | pmid=17018561 | doi=10.1136/jmg.2006.045328 | pmc=2598029 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17018561 }} </ref>. Dense deposit disease refers to one subcategory of C3 glomerulopathy which is characterized by GBM deposits of C3 with characteristic appearance on electron micro graphs. Isolated C3 deposit in the glomerulus is the defining characteristics of C3 glomerulopathy. When deposit is linear, ribbon like and concentrated on the glomerular basement membrane, it is referred to as the Dense Deposit Disease (DDD). Currently, it is unknown whether the distinction between C3 glomerulonephritis and DDD has any therapeutic or prognostic relevance.
*C3 Glomerulopathy may be classified according to [classification method] into 2 main subtypes/groups:
:*Dense Deposit Disease (DDD)
:*C3 Glomerulonephritis (C3GN)

Dense Deposit Disease (DDD) is more common in children, and is frequently associated with lipodystrophy.

==[[C3 glomerulopathy pathophysiology|Pathophysiology]]==

C3 glomerulopathy results from the appropriate or inappropriate activation of the alternative pathway of the complement system.

The appropriate activation of complement system is under general circumstances triggered by infection. The inappropriate activation can be due to inherited or acquired disorders of complement pathway. Either a gain of function of complement “activators”, or a loss of function of complement “inhibitors” can lead to an activation of complement alternative pathway.

Possible physiological and pathological activation mechanisms of the complement pathways which can contribute or lead to complement mediated glomerulopathy:

{| class="wikitable"
! colspan="2" |Activation of Classic Complement Pathway
!Activation of the Mannose-Binding-Lictin Pathway
! colspan="4" |Activation of Alternative Complement Pathway
|-
| colspan="2" |Acquired
|Acquired
| colspan="3" |Acquired
|Inherited
|-
|Infection
|Apoptosis and necrosis
|Infection
|Infection
|Autoimmune disorder
|Paraneoplastic
|Genetic mutations
|}
==[[C3 glomerulopathy causes|Causes]]==
Several genetic or acquired causes have been described to date:
* C3 mutations:
Mutations in C3 have been described, whereby the mutant protein is resistant to the inhibitory effects of Membrane Cofactor Protein (ref needed)
* Complement Factor H (CFH):
Like the majority of complement factors, CFH is a small glycoprotein which is produced in the liver, and circulates freely in the blood plasma (ref). Several mutation in the CFH gene have been identified (ref OMIM). While in type 1 mutations in this gene lead to a decrease in the level of functional CFH, the majority of mutations (type 2) do not affect the level of CFH, but rather decrease or diminish the function activity of this glycoprotein.
Autoantibodies against CFH have been identified in up to xx of cases (ref). Here, a binding of the antibody to the glycoproteins leads to functional inactivation and removal of CFH from the plasma.

* Complement Factor I (CFI):

* Membrane Cofactor Protein (MCP):
MCP is a transmembrane protein, expressed by all nucleated cells and located at the cell surfaces. Together with Complement Factor I (CFI), MCP is required for the inactivation of C3b, which otherwise may initiate the formation of membrane attack complex. Mutations in the MCP gene can, similar to mutations in CFH lead to both, either a decrease in synthesis and expression of this protein, or a decreased activity.

* C3 nephritic factor (C3bBb antibody)
* Factor H antibody
* Factor I antibody
* Factor H mutations
* Factor I mutations
* Factor B mutations
* CR1 mutations
* CFHRs mutations

* Dense Deposit Disease
==[[C3 glomerulopathy differential diagnosis|Differentiating C3 glomerulopathy from other Diseases]]==
C3 glomerulopathy is differentiated from other inflammatory glomerulopathies by the sole presence of C3 deposits without any immune-complex depositions.

==[[C3 glomerulopathy epidemiology and demographics|Epidemiology and Demographics]]==
C3 Glomerulopathies are rare, with the Dense deposit disease (DDD) affecting only about two to three people per one million <ref name="pmid17675665">{{cite journal| author=Smith RJ, Alexander J, Barlow PN, Botto M, Cassavant TL, Cook HT et al.| title=New approaches to the treatment of dense deposit disease. | journal=J Am Soc Nephrol | year= 2007 | volume= 18 | issue= 9 | pages= 2447-56 | pmid=17675665 | doi=10.1681/ASN.2007030356 | pmc=4853920 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17675665 }} </ref> and C3. Clinical presentation of C3 Glomerulopathies varies but diagnosis is by electron microscopy of kidney biopsy specimen.

==[[C3 glomerulopathy risk factors|Risk factors]]==

==[[C3 glomerulopathy screening|Screening]]==

==[[C3 glomerulopathy natural history|Natural History, Complications and Prognosis]]==

==Diagnosis==
[[C3 glomerulopathy history and symptoms| History and Symptoms]] | [[C3 glomerulopathy physical examination | Physical Examination]] | [[C3 glomerulopathy laboratory tests | Laboratory Findings]] | [[C3 glomerulopathy x ray|X ray]] | [[C3 glomerulopathy CT|CT]] | [[C3 glomerulopathy MRI|MRI]] | [[C3 glomerulopathy echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[C3 glomerulopathy other imaging studies|Other Imaging Studies]] | [[C3 glomerulopathy other diagnostic studies|Other Diagnostic Studies]]

==Treatment ==
[[C3 glomerulopathy surgery|Surgery]] | [[C3 glomerulopathy Medical therapy|Medical therapy]] | [[C3 glomerulopathy primary prevention|Primary Prevention]] | [[C3 glomerulopathy secondary prevention|Secondary Prevention]] | [[C3 glomerulopathy cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[C3 glomerulopathy future or investigational therapies|Future or Investigational Therapies]]

==Case Studies==
[[C3 glomerulopathy case study one|Case #1]]

==Classification==

==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

==Causes==

==Differentiating C3 Glomerulopathy from other Diseases==
*C3 glomerulopathy must be differentiated from other diseases that cause inflammatory glomerulonephritis with glomerular complement deposition such as:
:*Infection-related glomerulonephritis
:*Lupus nephritis
:*Paraprotein related glomerulonephritis.

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of C3 glomerulopathy is made by one of the following techniques:
:*C3 nephropathies are diagnosed by light and electron microscopy of kidney biopsy specimen. Electron microscopy can be used to differentiate DDD from other C3 Glomerulopathies.
:*Other specialized diagnostic techniques include: Serum C3 and C4 levels, Serum Protein Electrophoresis studies, Genetic screening.
:*The kidney biopsy and blood tests are currently done only in highly specialized laboratories.

=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of C3 glomerulopathy may include the following:
:*Foamy urine due proteinuria ( excessive protein in urine)or hematuria (blood in the urine)
:*Signs of renal insufficiency like general fatigue or malaise
:*Hypertension (especially in children is a red flag )
:*Low serum C3 level
:*Acquired lipodystrophy (loss of subcutaneous fat in the upper half of the body) in DDD
:*Macular (Drusen) deposits in the retina of the eye (also seen in DDD)

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*Treatment is based on type of C3 glomerulopathy, severity and available treatment modalities.
*Adequate control of proteinuria and hypertension is important. T.
*Patients with DDD or C3GN may be treated with lipid lowering medications to prevent cardiovascular events.
*All patients should be closely monitored with scheduled checkups and diagnostic laboratory workups.
*Genetic screening is also advised for family members of patients that have genetic mutations.
*Patients’ support groups can be found with groups like NEPHCURE Kidney International and other foundation that provide support for kidney patients and their families.

=== Prevention ===
*There are no primary preventive measures available for C3 glomerulopathy .

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

==References==
{{Reflist|2}}

[[Category:Nephrology]]

Paraprotein-related kidney disease

2017-03-09T21:06:16Z

Ali Poyan Mehr:

{{CMG}} {{APM}}

{{SK}} monoclonal gammopathy of renal significance; MGRS; paraproteinemia

==Overview==

Paraproteinemia refers to the presence of abnormal protein or protein fragments in the blood. The proteins referred to are immunoglobulins (or fragments of), and are of monoclonal origin (M-spike). Under certain circumstances these circulating monoclonal immunoglobulins are deposited in the renal tissues and can lead to various forms of renal disease.

==Historical Perspective==
In 1848, Henry Bence Jones (http://rstl.royalsocietypublishing.org/content/138/55) reported on the discovery of an "new substance" in the urine of an ill patient. Over the course of the history, this protein was termed "Bence Jones" and found to be associated with "myeloma". The term "myeloma kidney" was used first by Alfred von Decastello in 1909.

By 1939 the abnormal band described in serum electrophoresis of myeloma patients as "M-spike", was found to be due to immuneglobulin proteins.

Subsequent studies were able to further characterize these abnormal immunoglobulins and define as monoclonal kappa or lambda light chains, and confirm Bence Jones proteins to be the same as the circulating monoclonal immuneglobulins (para-proteins). (http://medcraveonline.com/UNOAJ/UNOAJ-03-00078.pdf)

==Classification==
*Paraprotein-related kidney disease may be classified according to the type of renal involvement and the underlying hematologic disorder into at least 10 various subtypes:
:* AL Amyloidosis (either due to lambda or kappa light chains (AL), or due to heavy chains (AH), or both (ALH))
:* Cryoglobulinemic GN, Waldenstrom type
:* Cryoglobulinemic GN, Multiple Myeloma
:* Cryglobulinemia type I or II: Ideopathic, lymphoma
:* Immunotactoid Glomerulopathy
:* Fibrillary Glomerulopathy
:* Light chain deposition disease
:* Heavy chain deposition disease
:* Mixed light and heavy chain deposition disease
:* Proliferative GN with monoclonal Ig
:* Cast nephropathy

==Pathophysiology==
Here, the pathophysiology of paraprotein-related kidney disease will be discussed. For the pathophysiology of clonal plasma cell or B-cell disorders, including multiple myeloma, please refer to the corresponding chapters.

Monoclonal gammopathies (abnormal amounts of immunoglobulins from a single B-cell clone) can reflect a disease process, but also be benign (PMID:10926917).

The most widely recognized renal disorders due to paraproteinemias is light chain cast nephropathy (PMID:25607108 )..

depending on the burden of the underlying plasma cell or B-cell clone. In the first group of renal disorders, large amounts of all or part of the MIg is secreted and is associated with a high tumor mass B-cell proliferation. This condition characterizes: 1- light-chain cast nephropathy, the most common cause of acute kidney injury in multiple myeloma (MM) and 2-thrombi in high tumor mass Waldenstrom’s macroglobulinemia. The second group of MIg-related renal lesions are mainly seen in patients with a small B-cell clone and low malignant potential. They may also occur during symptomatic B-cell proliferations (PMID:25607108 ).

Many of these nonmalignant clones are classified as: 1- monoclonal gammopathy of undetermined significance (MGUS- with <3 g/dl of monoclonal protein and <10% bone marrow plasma cells) or 2- smoldering MM (with >3 g/dl of monoclonal protein and/or >10% bone marrow plasma cells) and they do not produce any end organ damage.

While Monoclonal gammopathy of renal significance (MGRS) and Symptomatic MM are defined by evidence of end organ damage.

Clinical and biological surveillance is the only required treatment of MGUS, smoldering MM and low-grade lymphomas, because they may remain asymptomatic over a prolonged period of time and studies have shown chemotherapy not to be beneficial in the majority of patients.

MGRS is consistent with MGUS hematologic-wise but because of severe consequences produced in the kidneys (and sometimes in other organs), early detection and suppression of MIg secretion by chemotherapy is crucial in MGRS.

MGRS related kidney disorders include AL amyloidosis, proliferative glomerulonephritis with MIg deposits (PGNMID), C3 glomerulopathy with monoclonal gammopathy, light-chain deposition disease (LCDD) and immunotactoid glomerulopathy. Kidney biopsy is indicated in most cases. Other diagnostic ways include light microscopy, immunofluorescence (IF), electron microscopy, and in some cases IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Besides, complete hematologic workup with serum and urine protein electrophoresis, immunofixation, and serum-free light-chain assay is required (PMID:25607108).
* MGRS could also be caused by mechanisms other than deposition of MIg, which could be responsible for another spectrum of MGRS related kidney disorders (PMID:25607108).

The type of kidney involvement highly depends on the specific characteristics of the paraprotein.

:* AL Amyloidosis (either due to lambda or kappa light chains)
AL amyloidosis is caused by the deposition of amyloid deposits in extracellular spaces. These amyloid proteins are formed by light chains (hence AL for amyloid light chain) .These deposits may infiltrate the glomerular basement membrane or may be localized on both of its sides. Glomerular amyloid deposition produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney, often with heavy proteinuria. Immunoglobulin-Associated amyloidosis (AL amyloidosis) is the most frequent and severe form amyloidosis affecting the kidneys.

:* Cryoglobulinemic GN, Waldenstrom type

:* Cryoglobulinemic GN, Multiple Myeloma

:* Cryglobulinemia type I: Ideopathic

:* Immunotactoid Glomerulopathy

:* Fibrillary Glomerulopathy

:* Monoclonal immunoglobulin deposition disease, including light chain deposition disease and heavy chain deposition disease:
Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

:* Proliferative GN with monoclonal Ig

:* Cast nephropathy

==Causes==

Para-protein-related kidney disease can be caused by all many forms of plasma cell neoplasms ad B-cell lympho-proliferative disorders. These include:

Plasma cell neoplasms:

Smoldering myeloma (defined as: ____)

Multiple Myeloma (defined as___)

Plasmocytoma

B-Cell lymphoma

'''AL Amyloidosis''':

AL Amyloidosis is is caused by the deposition of Amyloid deposits in extracellular spaces which could affect various organs. Albeit, the precursor proteins are different but they all have unique Congo red staining characteristics which is because of the same antiparallel beta pleated sheet configuration on X-ray diffraction.

All types of amyloid contain a 25Kdglycoprotein, serum amyloid P component (SAP) and C-reactive protein. Subsets of heparin and dermatan sulfated glycosaminoglycan (GAGS) and proteoglycans may be found in amyloid deposits. In AL amyloidosis, plasma cells produce variable portion of immunoglobulin light chains which are the source of amyloid fibrils.

* These deposits may infiltrate the glomerular basement membrane (GMB) or may be localized on both its sides. Advanced amyloid produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney. The most frequent and severe amyloidosis affecting the kidney is Immunoglobulin-Associated amyloidosis (AL amyloidosis). may be caused by either [cause1], [cause2], or [cause3].
* [Disease name] Fibrillary Glomerulopathy is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

*

* There are no established causes f or [disease name].
* Cast nephropathy which is the most common form of kidney disease in patients with MM is occurred because of coprecipitation of immunoglobulin free light chains (FLCs) with Tamm-Horsfall glycoprotein (THP). this consequently causes the obstruction of the ascending limb of the loop of Henle, and the rapid decline in renal function (Treating myeloma cast nephropathy without treating myeloma).
* clonal proliferation of immunoglobulin-producing plasma cells is the cause of multiple
myeloma and monoclonal gammopathy of undetermined significance (MGUS). These neoplastic cells stop synthesizing the normal heavy chain component of the immunoglobulin molecule and start secreting only k or l light chains (Monoclonal Gammopathy-Associated Proliferative Glomerulonephritis).

monoclonal gammopathies of renal significance (MGRS), is kidney diseases due to monoclonal Ig (MIg) deposition but do not meet criteria for overt multiple myeloma (Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal Significance).

MGUS/smoldering MM and MGRS are distinguished not by the quantity of the plasma cell clone and its

secreted paraprotein, but by whether it results in end organ damage.

==Differentiating Paraprotein related kidney disease from other diseases==
:*

==Epidemiology and Demographics==
*

===Age===
*

===Gender===
*

===Race===
*

==Risk Factors==
*

== Natural History, Complications and Prognosis==
*

== Diagnosis ==
===Diagnostic Criteria===
:*

=== Symptoms ===
*Cryoglobulinemic GN, Waldenstrom type is presented by:fatigue,weight loss,bleeding, visual disturbances, peripheral neuropathy, hepatosplenomegaly, lymphadenopathy, anemia and hyperviscosity syndrome.
Renal involvement in Waldenstrom macroglobulinemia is uncommon but glomerular lesions are found in some patients. Which is manifested by microscopic hematuria and proteinuria, and renal failure.

=== Physical Examination ===
:*

=== Laboratory Findings ===
For the work-up of monoclonal immunoglobulin depositions in the glomerulus one may consider the following:
* Serum and urine protein electrophoresis are good starter, but least sensitive test (Sensitivity of SPEP ~88% in patients with MM, ~66% in AL amyloidosis, ~56% in light chain deposition disease, and 15% in monoclonal gammopathy related GN)
* Serum and urine immunofixation may significantly increase the sensitivity of detecting monoclonal paraproteins.
* Additional serum free light chain assay (most sensitive test), and a skewed kappa/lambda ratio can further point toward an abnormal production of either of them (ration is also affected in CKD and infection!).
* Flow cytometry of bone marrow (+/- peripheral blood) may further help identify to source of the monoclonal Ig production. Be aware that neoplastic clones producing monoclonal Ig can be plasma cell clones (multiple myeloma), as well as B cell clones (B-cell lymphoma, CLL, Waldenstrom macroglobulinemia).

===Imaging Findings===
*

=== Other Diagnostic Studies ===
*

== Treatment ==
=== Medical Therapy ===
*Treatment options for monoclonal gammopathies of renal significance are borrowed from guidelines and protocols used for hematological malignancies, and based on anecdotal experiences and retrospective case reviews. This may include: Combination therapy for plasma cell depletion with bortezomib, cyclophosphamide, and dexamethasone for NON-IgM type monoclonal Ig deposits in glomerulus. Combination or single agent therapy for B-cell depletion with rituximab or cyclophosphamide in case of IgM type deposition.
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Paraprotein-related kidney disease

2017-03-09T21:05:03Z

Ali Poyan Mehr:

{{CMG}} {{APM}}

{{SK}} monoclonal gammopathy of renal significance; MGRS; paraproteinemia

==Overview==

Paraproteinemia refers to the presence of abnormal protein or protein fragments in the blood. The proteins referred to are immunoglobulins (or fragments of), and are of monoclonal origin (M-spike). Under certain circumstances these circulating monoclonal immunoglobulins are deposited in the renal tissues and can lead to various forms of renal disease.

==Historical Perspective==
In 1848, Henry Bence Jones (http://rstl.royalsocietypublishing.org/content/138/55) reported on the discovery of an "new substance" in the urine of an ill patient. Over the course of the history, this protein was termed "Bence Jones" and found to be associated with "myeloma". The term "myeloma kidney" was used first by Alfred von Decastello in 1909.

By 1939 the abnormal band described in serum electrophoresis of myeloma patients as "M-spike", was found to be due to immuneglobulin proteins.

Subsequent studies were able to further characterize these abnormal immunoglobulins and define as monoclonal kappa or lambda light chains, and confirm Bence Jones proteins to be the same as the circulating monoclonal immuneglobulins (para-proteins). (http://medcraveonline.com/UNOAJ/UNOAJ-03-00078.pdf)

==Classification==
*Paraprotein-related kidney disease may be classified according to the type of renal involvement and the underlying hematologic disorder into at least 10 various subtypes:
:* AL Amyloidosis (either due to lambda or kappa light chains (AL), or due to heavy chains (AH), or both (ALH))
:* Cryoglobulinemic GN, Waldenstrom type
:* Cryoglobulinemic GN, Multiple Myeloma
:* Cryglobulinemia type I or II: Ideopathic, lymphoma
:* Immunotactoid Glomerulopathy
:* Fibrillary Glomerulopathy
:* Light chain deposition disease
:* Heavy chain deposition disease
:* Mixed light and heavy chain deposition disease
:* Proliferative GN with monoclonal Ig
:* Cast nephropathy

==Pathophysiology==
Here, the pathophysiology of paraprotein-related kidney disease will be discussed. For the pathophysiology of clonal plasma cell or B-cell disorders, including multiple myeloma, please refer to the corresponding chapters.

Monoclonal gammopathies (abnormal amounts of immunoglobulins from a single B-cell clone) can reflect a disease process, but also be benign (PMID:10926917).

The most widely recognized renal disorders due to paraproteinemias is light chain cast nephropathy (PMID:25607108 )..

depending on the burden of the underlying plasma cell or B-cell clone. In the first group of renal disorders, large amounts of all or part of the MIg is secreted and is associated with a high tumor mass B-cell proliferation. This condition characterizes: 1- light-chain cast nephropathy, the most common cause of acute kidney injury in multiple myeloma (MM) and 2-thrombi in high tumor mass Waldenstrom’s macroglobulinemia. The second group of MIg-related renal lesions are mainly seen in patients with a small B-cell clone and low malignant potential. They may also occur during symptomatic B-cell proliferations (PMID:25607108 ).

Many of these nonmalignant clones are classified as: 1- monoclonal gammopathy of undetermined significance (MGUS- with <3 g/dl of monoclonal protein and <10% bone marrow plasma cells) or 2- smoldering MM (with >3 g/dl of monoclonal protein and/or >10% bone marrow plasma cells) and they do not produce any end organ damage.

While Monoclonal gammopathy of renal significance (MGRS) and Symptomatic MM are defined by evidence of end organ damage.

Clinical and biological surveillance is the only required treatment of MGUS, smoldering MM and low-grade lymphomas, because they may remain asymptomatic over a prolonged period of time and studies have shown chemotherapy not to be beneficial in the majority of patients.

MGRS is consistent with MGUS hematologic-wise but because of severe consequences produced in the kidneys (and sometimes in other organs), early detection and suppression of MIg secretion by chemotherapy is crucial in MGRS.

MGRS related kidney disorders include AL amyloidosis, proliferative glomerulonephritis with MIg deposits (PGNMID), C3 glomerulopathy with monoclonal gammopathy, light-chain deposition disease (LCDD) and immunotactoid glomerulopathy. Kidney biopsy is indicated in most cases. Other diagnostic ways include light microscopy, immunofluorescence (IF), electron microscopy, and in some cases IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Besides, complete hematologic workup with serum and urine protein electrophoresis, immunofixation, and serum-free light-chain assay is required (PMID:25607108).
* MGRS could also be caused by mechanisms other than deposition of MIg, which could be responsible for another spectrum of MGRS related kidney disorders (PMID:25607108).

The type of kidney involvement highly depends on the specific characteristics of the paraprotein.

:* AL Amyloidosis (either due to lambda or kappa light chains)
AL amyloidosis is caused by the deposition of amyloid deposits in extracellular spaces. These amyloid proteins are formed by light chains (hence AL for amyloid light chain) .These deposits may infiltrate the glomerular basement membrane or may be localized on both of its sides. Glomerular amyloid deposition produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney, often with heavy proteinuria. Immunoglobulin-Associated amyloidosis (AL amyloidosis) is the most frequent and severe form amyloidosis affecting the kidneys.

:* Cryoglobulinemic GN, Waldenstrom type

:* Cryoglobulinemic GN, Multiple Myeloma

:* Cryglobulinemia type I: Ideopathic

:* Immunotactoid Glomerulopathy

:* Fibrillary Glomerulopathy

:* Monoclonal immunoglobulin deposition disease, including light chain deposition disease and heavy chain deposition disease:
Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

:* Proliferative GN with monoclonal Ig

:* Cast nephropathy

==Causes==

Para-protein-related kidney disease can be caused by all many forms of plasma cell neoplasms ad B-cell lympho-proliferative disorders. These include:

Plasma cell neoplasms:

Smoldering myeloma (defined as: ____)

Multiple Myeloma (defined as___)

Plasmocytoma

B-Cell lymphoma

'''AL Amyloidosis''':

AL Amyloidosis is is caused by the deposition of Amyloid deposits in extracellular spaces which could affect various organs. Albeit, the precursor proteins are different but they all have unique Congo red staining characteristics which is because of the same antiparallel beta pleated sheet configuration on X-ray diffraction.

All types of amyloid contain a 25Kdglycoprotein, serum amyloid P component (SAP) and C-reactive protein. Subsets of heparin and dermatan sulfated glycosaminoglycan (GAGS) and proteoglycans may be found in amyloid deposits. In AL amyloidosis, plasma cells produce variable portion of immunoglobulin light chains which are the source of amyloid fibrils.

* These deposits may infiltrate the glomerular basement membrane (GMB) or may be localized on both its sides. Advanced amyloid produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney. The most frequent and severe amyloidosis affecting the kidney is Immunoglobulin-Associated amyloidosis (AL amyloidosis). may be caused by either [cause1], [cause2], or [cause3].
* [Disease name] Fibrillary Glomerulopathy is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

*

* There are no established causes f or [disease name].
* Cast nephropathy which is the most common form of kidney disease in patients with MM is occurred because of coprecipitation of immunoglobulin free light chains (FLCs) with Tamm-Horsfall glycoprotein (THP). this consequently causes the obstruction of the ascending limb of the loop of Henle, and the rapid decline in renal function (Treating myeloma cast nephropathy without treating myeloma).
* clonal proliferation of immunoglobulin-producing plasma cells is the cause of multiple
myeloma and monoclonal gammopathy of undetermined significance (MGUS). These neoplastic cells stop synthesizing the normal heavy chain component of the immunoglobulin molecule and start secreting only k or l light chains (Monoclonal Gammopathy-Associated Proliferative Glomerulonephritis).

monoclonal gammopathies of renal significance (MGRS), is kidney diseases due to monoclonal Ig (MIg) deposition but do not meet criteria for overt multiple myeloma (Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal Significance).

MGUS/smoldering MM and MGRS are distinguished not by the quantity of the plasma cell clone and its

secreted paraprotein, but by whether it results in end organ damage.

==Differentiating Paraprotein related kidney disease from other diseases==
:*

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*Cryoglobulinemic GN, Waldenstrom type is presented by:fatigue,weight loss,bleeding, visual disturbances, peripheral neuropathy, hepatosplenomegaly, lymphadenopathy, anemia and hyperviscosity syndrome.
Renal involvement in Waldenstrom macroglobulinemia is uncommon but glomerular lesions are found in some patients. Which is manifested by microscopic hematuria and proteinuria, and renal failure.

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
For the work-up of monoclonal immunoglobulin depositions in the glomerulus one may consider the following:
* Serum and urine protein electrophoresis are good starter, but least sensitive test (Sensitivity of SPEP ~88% in patients with MM, ~66% in AL amyloidosis, ~56% in light chain deposition disease, and 15% in monoclonal gammopathy related GN)
* Serum and urine immunofixation may significantly increase the sensitivity of detecting monoclonal paraproteins.
* Additional serum free light chain assay (most sensitive test), and a skewed kappa/lambda ratio can further point toward an abnormal production of either of them (ration is also affected in CKD and infection!).
* Flow cytometry of bone marrow (+/- peripheral blood) may further help identify to source of the monoclonal Ig production. Be aware that neoplastic clones producing monoclonal Ig can be plasma cell clones (multiple myeloma), as well as B cell clones (B-cell lymphoma, CLL, Waldenstrom macroglobulinemia).

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*Treatment options for monoclonal gammopathies of renal significance are borrowed from guidelines and protocols used for hematological malignancies, and based on anecdotal experiences and retrospective case reviews. This may include: Combination therapy for plasma cell depletion with bortezomib, cyclophosphamide, and dexamethasone for NON-IgM type monoclonal Ig deposits in glomerulus. Combination or single agent therapy for B-cell depletion with rituximab or cyclophosphamide in case of IgM type deposition.
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Paraprotein-related kidney disease

2017-03-09T21:03:48Z

Ali Poyan Mehr:

{{CMG}} {{APM}}

{{SK}} monoclonal gammopathy of renal significance; MGRS; paraproteinemia

==Overview==

Paraproteinemia refers to the presence of abnormal protein or protein fragments in the blood. The proteins referred to are immunoglobulins (or fragments of), and are of monoclonal origin (M-spike). Under certain circumstances these circulating monoclonal immunoglobulins are deposited in the renal tissues and can lead to various forms of renal disease.

==Historical Perspective==
In 1848, Henry Bence Jones (http://rstl.royalsocietypublishing.org/content/138/55) reported on the discovery of an "new substance" in the urine of an ill patient. Over the course of the history, this protein was termed "Bence Jones" and found to be associated with "myeloma". The term "myeloma kidney" was used first by Alfred von Decastello in 1909.

By 1939 the abnormal band described in serum electrophoresis of myeloma patients as "M-spike", was found to be due to immuneglobulin proteins.

Subsequent studies were able to further characterize these abnormal immunoglobulins and define as monoclonal kappa or lambda light chains, and confirm Bence Jones proteins to be the same as the circulating monoclonal immuneglobulins (para-proteins). (http://medcraveonline.com/UNOAJ/UNOAJ-03-00078.pdf)

==Classification==
*Paraprotein-related kidney disease may be classified according to the type of renal involvement and the underlying hematologic disorder into at least 10 various subtypes:
:* AL Amyloidosis (either due to lambda or kappa light chains (AL), or due to heavy chains (AH), or both (ALH))
:* Cryoglobulinemic GN, Waldenstrom type
:* Cryoglobulinemic GN, Multiple Myeloma
:* Cryglobulinemia type I or II: Ideopathic, lymphoma
:* Immunotactoid Glomerulopathy
:* Fibrillary Glomerulopathy
:* Light chain deposition disease
:* Heavy chain deposition disease
:* Mixed light and heavy chain deposition disease
:* Proliferative GN with monoclonal Ig
:* Cast nephropathy

==Pathophysiology==
Here, the pathophysiology of paraprotein-related kidney disease will be discussed. For the pathophysiology of clonal plasma cell or B-cell disorders, including multiple myeloma, please refer to the corresponding chapters.

Monoclonal gammopathies (abnormal amounts of immunoglobulins from a single B-cell clone) can reflect a disease process, but also be benign (PMID:10926917).

The most widely recognized renal disorders due to paraproteinemias is light chain cast nephropathy (PMID:25607108 )..

depending on the burden of the underlying plasma cell or B-cell clone. In the first group of renal disorders, large amounts of all or part of the MIg is secreted and is associated with a high tumor mass B-cell proliferation. This condition characterizes: 1- light-chain cast nephropathy, the most common cause of acute kidney injury in multiple myeloma (MM) and 2-thrombi in high tumor mass Waldenstrom’s macroglobulinemia. The second group of MIg-related renal lesions are mainly seen in patients with a small B-cell clone and low malignant potential. They may also occur during symptomatic B-cell proliferations (PMID:25607108 ).

Many of these nonmalignant clones are classified as: 1- monoclonal gammopathy of undetermined significance (MGUS- with <3 g/dl of monoclonal protein and <10% bone marrow plasma cells) or 2- smoldering MM (with >3 g/dl of monoclonal protein and/or >10% bone marrow plasma cells) and they do not produce any end organ damage.

While Monoclonal gammopathy of renal significance (MGRS) and Symptomatic MM are defined by evidence of end organ damage.

Clinical and biological surveillance is the only required treatment of MGUS, smoldering MM and low-grade lymphomas, because they may remain asymptomatic over a prolonged period of time and studies have shown chemotherapy not to be beneficial in the majority of patients.

MGRS is consistent with MGUS hematologic-wise but because of severe consequences produced in the kidneys (and sometimes in other organs), early detection and suppression of MIg secretion by chemotherapy is crucial in MGRS.

MGRS related kidney disorders include AL amyloidosis, proliferative glomerulonephritis with MIg deposits (PGNMID), C3 glomerulopathy with monoclonal gammopathy, light-chain deposition disease (LCDD) and immunotactoid glomerulopathy. Kidney biopsy is indicated in most cases. Other diagnostic ways include light microscopy, immunofluorescence (IF), electron microscopy, and in some cases IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Besides, complete hematologic workup with serum and urine protein electrophoresis, immunofixation, and serum-free light-chain assay is required (PMID:25607108).
* MGRS could also be caused by mechanisms other than deposition of MIg, which could be responsible for another spectrum of MGRS related kidney disorders (PMID:25607108).

The type of kidney involvement highly depends on the specific characteristics of the paraprotein.

:* AL Amyloidosis (either due to lambda or kappa light chains)
AL amyloidosis is caused by the deposition of amyloid deposits in extracellular spaces. These amyloid proteins are formed by light chains (hence AL for amyloid light chain) .These deposits may infiltrate the glomerular basement membrane or may be localized on both of its sides. Glomerular amyloid deposition produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney, often with heavy proteinuria. Immunoglobulin-Associated amyloidosis (AL amyloidosis) is the most frequent and severe form amyloidosis affecting the kidneys.

:* Cryoglobulinemic GN, Waldenstrom type

:* Cryoglobulinemic GN, Multiple Myeloma

:* Cryglobulinemia type I: Ideopathic

:* Immunotactoid Glomerulopathy

:* Fibrillary Glomerulopathy

:* Monoclonal immunoglobulin deposition disease, including light chain deposition disease and heavy chain deposition disease:
Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

:* Proliferative GN with monoclonal Ig

:* Cast nephropathy

==Causes==

Para-protein-related kidney disease can be caused by all many forms of plasma cell neoplasms ad B-cell lympho-proliferative disorders. These include:

Plasma cell neoplasms:

Smoldering myeloma (defined as: ____)

Multiple Myeloma (defined as___)

Plasmocytoma

B-Cell lymphoma

'''AL Amyloidosis''':

AL Amyloidosis is is caused by the deposition of Amyloid deposits in extracellular spaces which could affect various organs. Albeit, the precursor proteins are different but they all have unique Congo red staining characteristics which is because of the same antiparallel beta pleated sheet configuration on X-ray diffraction.

All types of amyloid contain a 25Kdglycoprotein, serum amyloid P component (SAP) and C-reactive protein. Subsets of heparin and dermatan sulfated glycosaminoglycan (GAGS) and proteoglycans may be found in amyloid deposits. In AL amyloidosis, plasma cells produce variable portion of immunoglobulin light chains which are the source of amyloid fibrils.

* These deposits may infiltrate the glomerular basement membrane (GMB) or may be localized on both its sides. Advanced amyloid produces a nonproliferative, noninflammatory glomerulopathy and enlargement of the kidney. The most frequent and severe amyloidosis affecting the kidney is Immunoglobulin-Associated amyloidosis (AL amyloidosis). may be caused by either [cause1], [cause2], or [cause3].
* [Disease name] Fibrillary Glomerulopathy is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* Monoclonal immunoglobulin deposition disease(MIDD) includes light chain deposition disease (LCDD) as the most common pattern, heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LCDD/HCDD). MIDD is caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin protein. These deposits in LCDD are composed of kappa rather than lambda light chains in approximately 80% of cases.

*

* There are no established causes f or [disease name].
* Cast nephropathy which is the most common form of kidney disease in patients with MM is occurred because of coprecipitation of immunoglobulin free light chains (FLCs) with Tamm-Horsfall glycoprotein (THP). this consequently causes the obstruction of the ascending limb of the loop of Henle, and the rapid decline in renal function (Treating myeloma cast nephropathy without treating myeloma).
* clonal proliferation of immunoglobulin-producing plasma cells is the cause of multiple
myeloma and monoclonal gammopathy of undetermined significance (MGUS). These neoplastic cells stop synthesizing the normal heavy chain component of the immunoglobulin molecule and start secreting only k or l light chains (Monoclonal Gammopathy-Associated Proliferative Glomerulonephritis).

monoclonal gammopathies of renal significance (MGRS), is kidney diseases due to monoclonal Ig (MIg) deposition but do not meet criteria for overt multiple myeloma (Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal Significance).

MGUS/smoldering MM and MGRS are distinguished not by the quantity of the plasma cell clone and its

secreted paraprotein, but by whether it results in end organ damage.

==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*Cryoglobulinemic GN, Waldenstrom type is presented by:fatigue,weight loss,bleeding, visual disturbances, peripheral neuropathy, hepatosplenomegaly, lymphadenopathy, anemia and hyperviscosity syndrome.
Renal involvement in Waldenstrom macroglobulinemia is uncommon but glomerular lesions are found in some patients. Which is manifested by microscopic hematuria and proteinuria, and renal failure.

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
For the work-up of monoclonal immunoglobulin depositions in the glomerulus one may consider the following:
* Serum and urine protein electrophoresis are good starter, but least sensitive test (Sensitivity of SPEP ~88% in patients with MM, ~66% in AL amyloidosis, ~56% in light chain deposition disease, and 15% in monoclonal gammopathy related GN)
* Serum and urine immunofixation may significantly increase the sensitivity of detecting monoclonal paraproteins.
* Additional serum free light chain assay (most sensitive test), and a skewed kappa/lambda ratio can further point toward an abnormal production of either of them (ration is also affected in CKD and infection!).
* Flow cytometry of bone marrow (+/- peripheral blood) may further help identify to source of the monoclonal Ig production. Be aware that neoplastic clones producing monoclonal Ig can be plasma cell clones (multiple myeloma), as well as B cell clones (B-cell lymphoma, CLL, Waldenstrom macroglobulinemia).

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*Treatment options for monoclonal gammopathies of renal significance are borrowed from guidelines and protocols used for hematological malignancies, and based on anecdotal experiences and retrospective case reviews. This may include: Combination therapy for plasma cell depletion with bortezomib, cyclophosphamide, and dexamethasone for NON-IgM type monoclonal Ig deposits in glomerulus. Combination or single agent therapy for B-cell depletion with rituximab or cyclophosphamide in case of IgM type deposition.
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-03-09T20:54:18Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{CMG}} {{APM}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
=== Laboratory Findings ===
*
===Imaging Findings===
*

=== Other Diagnostic Studies ===
*

== Treatment ==
=== Medical Therapy ===
*

=== Surgery ===
*

=== Prevention ===
*
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-03-09T20:52:32Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{CMG}} {{APM}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
=== Laboratory Findings ===
*
===Imaging Findings===
*

=== Other Diagnostic Studies ===
*

== Treatment ==
=== Medical Therapy ===
*

=== Surgery ===
*

=== Prevention ===
*
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

C3 glomerulopathy

2017-03-09T20:46:35Z

Ali Poyan Mehr:

__NOTOC__
{{C3 glomerulopathy}}
{{CMG}} {{APM}} {{AE}}

{{SK}} glomerulonephritis; C3 glomerulonephritis; dense deposit disease

==[[C3 glomerulopathy overview|Overview]]==
C3 glomerulopathy is a disorder of complement system, and can be due to inherited or acquired complement dysregulation and activation of the "alternative pathway". The category of C3 glomerulopathy contains a diverse group of disorders, including those leading to the inflammatory forms of C3 glomerulopathy, namely C3 glomerulonephritis (C3GN), as wells as those presenting as dense deposit disease (DDD). Both, C3GN and DDD are marked by C3 deposition along the capillary loop, the basement membrane, and the mesangium. It is a requirement for the diagnosis of C3 glomerulopathy, that the presence of C3 deposits comes without any concomitant immunoglobulin deposition.

The activation of the alternative pathway of the complement system can be either due to inherited, or acquired defects of the complement system. The inherited forms of complement dysregulation are due to numerous identified (and potentially yet to be identified) mutations of genes involved in complement pathway (see causes). The acquired forms of complement dysregulation are mostly due to autoimmunity against complement regulatory proteins.

==[[C3 glomerulopathy historical perspective|Historical Perspective]]==
In 1915 William C. Gunn reported on the finding of low circulating complement levels in patients with acute infection and nephritic presentation (DOI: 10.1002/path.1700190202). Later on, additional reports on the involvement of complement system in other forms of inflammatory glomerulonephritis were presented, and their role further established (PMID:13568372) (PMID: 14201535) <ref name="pmid14461382">{{cite journal| author=LACHMANN PJ, MULLER-EBERHARD HJ, KUNKEL HG, PARONETTO F| title=The localization of in vivo bound complement in tissue section. | journal=J Exp Med | year= 1962 | volume= 115 | issue= | pages= 63-82 | pmid=14461382 | doi= | pmc=2137475 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14461382 }} </ref>. In the year 1962, two renowned Nephro-pathologists, Jean Berger and Pierre Galle identified a rare glomerular lesion characterized by dense intramembranous deposits on transmission EM <ref name="pmid13867660">{{cite journal| author=BERGER J, GALLE P| title=[Unusual change of the basal membranes of the kidney]. | journal=J Urol Nephrol (Paris) | year= 1962 | volume= 68 | issue= | pages= 116-22 | pmid=13867660 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13867660 }} </ref>. The term Dense Deposit Disease (DDD) was coined and described to be a disease entity associated with under belonging to the category of membrano-proliferative type glomerulonephritides (MPGN) (Mathew TH, Kincaid-Smith P). It took almost 50 years, until C3 glomerulopathy was identified as an independent disease entity, leading to potentially new diagnostic, therapeutic and prognostic opportunities <ref name="pmid170185612">{{cite journal| author=Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B et al.| title=Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. | journal=J Med Genet | year= 2007 | volume= 44 | issue= 3 | pages= 193-9 | pmid=17018561 | doi=10.1136/jmg.2006.045328 | pmc=2598029 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17018561 }}</ref> (PMID: 20606628).

==[[C3 glomerulopathy classification|Classification]]==
Until recently, C3 glomerulopathy (C3 glomerulonephritis and DDD) were categorized under as a variant of MPGN, namely MPGN type 2 (PMID: 15800116). In 2007, Servais A. et al described C3GN as an entity by itself. C3 glomerulonephritis was described as glomerular disease with deposits made up of only C3 without the presence of any immunoglobulins, that may or may not have a membranoproliferative pattern <ref name="pmid17018561">{{cite journal| author=Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B et al.| title=Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. | journal=J Med Genet | year= 2007 | volume= 44 | issue= 3 | pages= 193-9 | pmid=17018561 | doi=10.1136/jmg.2006.045328 | pmc=2598029 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17018561 }} </ref>. Dense deposit disease refers to one subcategory of C3 glomerulopathy which is characterized by GBM deposits of C3 with characteristic appearance on electron micro graphs. Isolated C3 deposit in the glomerulus is the defining characteristics of C3 glomerulopathy. When deposit is linear, ribbon like and concentrated on the glomerular basement membrane, it is referred to as the Dense Deposit Disease (DDD). Currently, it is unknown whether the distinction between C3 glomerulonephritis and DDD has any therapeutic or prognostic relevance.
*C3 Glomerulopathy may be classified according to [classification method] into 2 main subtypes/groups:
:*Dense Deposit Disease (DDD)
:*C3 Glomerulonephritis (C3GN)

Dense Deposit Disease (DDD) is more common in children, and is frequently associated with lipodystrophy.

==[[C3 glomerulopathy pathophysiology|Pathophysiology]]==

C3 glomerulopathy results from the appropriate or inappropriate activation of the alternative pathway of the complement system.

The appropriate activation of complement system is under general circumstances triggered by infection. The inappropriate activation can be due to inherited or acquired disorders of complement pathway. Either a gain of function of complement “activators”, or a loss of function of complement “inhibitors” can lead to an activation of complement alternative pathway.

Possible physiological and pathological activation mechanisms of the complement pathways which can contribute or lead to complement mediated glomerulopathy:

{| class="wikitable"
! colspan="2" |Activation of Classic Complement Pathway
!Activation of the Mannose-Binding-Lictin Pathway
! colspan="4" |Activation of Alternative Complement Pathway
|-
| colspan="2" |Acquired
|Acquired
| colspan="3" |Acquired
|Inherited
|-
|Infection
|Apoptosis and necrosis
|Infection
|Infection
|Autoimmune disorder
|Paraneoplastic
|Genetic mutations
|}
==[[C3 glomerulopathy causes|Causes]]==
Several genetic or acquired causes have been described to date:
* C3 mutations:
Mutations in C3 have been described, whereby the mutant protein is resistant to the inhibitory effects of Membrane Cofactor Protein (ref needed)
* Complement Factor H (CFH):
Like the majority of complement factors, CFH is a small glycoprotein which is produced in the liver, and circulates freely in the blood plasma (ref). Several mutation in the CFH gene have been identified (ref OMIM). While in type 1 mutations in this gene lead to a decrease in the level of functional CFH, the majority of mutations (type 2) do not affect the level of CFH, but rather decrease or diminish the function activity of this glycoprotein.
Autoantibodies against CFH have been identified in up to xx of cases (ref). Here, a binding of the antibody to the glycoproteins leads to functional inactivation and removal of CFH from the plasma.

* Complement Factor I (CFI):

* Membrane Cofactor Protein (MCP):
MCP is a transmembrane protein, expressed by all nucleated cells and located at the cell surfaces. Together with Complement Factor I (CFI), MCP is required for the inactivation of C3b, which otherwise may initiate the formation of membrane attack complex. Mutations in the MCP gene can, similar to mutations in CFH lead to both, either a decrease in synthesis and expression of this protein, or a decreased activity.

* C3 nephritic factor (C3bBb antibody)
* Factor H antibody
* Factor I antibody
* Factor H mutations
* Factor I mutations
* Factor B mutations
* CR1 mutations
* CFHRs mutations

* Dense Deposit Disease
==[[C3 glomerulopathy differential diagnosis|Differentiating C3 glomerulopathy from other Diseases]]==
C3 glomerulopathy is differentiated from other inflammatory glomerulopathies by the sole presence of C3 deposits without any immune-complex depositions.

==[[C3 glomerulopathy epidemiology and demographics|Epidemiology and Demographics]]==
C3 Glomerulopathies are rare, with the Dense deposit disease (DDD) affecting only about two to three people per one million <ref name="pmid17675665">{{cite journal| author=Smith RJ, Alexander J, Barlow PN, Botto M, Cassavant TL, Cook HT et al.| title=New approaches to the treatment of dense deposit disease. | journal=J Am Soc Nephrol | year= 2007 | volume= 18 | issue= 9 | pages= 2447-56 | pmid=17675665 | doi=10.1681/ASN.2007030356 | pmc=4853920 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17675665 }} </ref> and C3. Clinical presentation of C3 Glomerulopathies varies but diagnosis is by electron microscopy of kidney biopsy specimen.

==[[C3 glomerulopathy risk factors|Risk factors]]==

==[[C3 glomerulopathy screening|Screening]]==

==[[C3 glomerulopathy natural history|Natural History, Complications and Prognosis]]==

==Diagnosis==
[[C3 glomerulopathy history and symptoms| History and Symptoms]] | [[C3 glomerulopathy physical examination | Physical Examination]] | [[C3 glomerulopathy laboratory tests | Laboratory Findings]] | [[C3 glomerulopathy x ray|X ray]] | [[C3 glomerulopathy CT|CT]] | [[C3 glomerulopathy MRI|MRI]] | [[C3 glomerulopathy echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[C3 glomerulopathy other imaging studies|Other Imaging Studies]] | [[C3 glomerulopathy other diagnostic studies|Other Diagnostic Studies]]

==Treatment ==
[[C3 glomerulopathy surgery|Surgery]] | [[C3 glomerulopathy Medical therapy|Medical therapy]] | [[C3 glomerulopathy primary prevention|Primary Prevention]] | [[C3 glomerulopathy secondary prevention|Secondary Prevention]] | [[C3 glomerulopathy cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[C3 glomerulopathy future or investigational therapies|Future or Investigational Therapies]]

==Case Studies==
[[C3 glomerulopathy case study one|Case #1]]

==Classification==

==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

==Causes==

==Differentiating C3 Glomerulopathy from other Diseases==
*C3 glomerulopathy must be differentiated from other diseases that cause inflammatory glomerulonephritis with glomerular complement deposition such as:
:*Infection-related glomerulonephritis
:*Lupus nephritis
:*Paraprotein related glomerulonephritis.

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of C3 glomerulopathy is made by one of the following techniques:
:*C3 nephropathies are diagnosed by light and electron microscopy of kidney biopsy specimen. Electron microscopy can be used to differentiate DDD from other C3 Glomerulopathies.
:*Other specialized diagnostic techniques include: Serum C3 and C4 levels, Serum Protein Electrophoresis studies, Genetic screening.
:*The kidney biopsy and blood tests are currently done only in highly specialized laboratories.

=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of C3 glomerulopathy may include the following:
:*Foamy urine due proteinuria ( excessive protein in urine)or hematuria (blood in the urine)
:*Signs of renal insufficiency like general fatigue or malaise
:*Hypertension (especially in children is a red flag )
:*Low serum C3 level
:*Acquired lipodystrophy (loss of subcutaneous fat in the upper half of the body) in DDD
:*Macular (Drusen) deposits in the retina of the eye (also seen in DDD)

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*Treatment is based on type of C3 glomerulopathy, severity and available treatment modalities.
*Adequate control of proteinuria and hypertension is important. T.
*Patients with DDD or C3GN may be treated with lipid lowering medications to prevent cardiovascular events.
*All patients should be closely monitored with scheduled checkups and diagnostic laboratory workups.
*Genetic screening is also advised for family members of patients that have genetic mutations.
*Patients’ support groups can be found with groups like NEPHCURE Kidney International and other foundation that provide support for kidney patients and their families.

=== Prevention ===
*There are no primary preventive measures available for C3 glomerulopathy .

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

==References==
{{Reflist|2}}

[[Category:Nephrology]]

Familial Hematuria & Hereditary Nephritis

2017-03-09T20:39:32Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
=== Laboratory Findings ===
*
===Imaging Findings===
*

=== Other Diagnostic Studies ===
*

== Treatment ==
=== Medical Therapy ===
*

=== Surgery ===
*

=== Prevention ===
*
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-13T23:29:38Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
**[symptom 1]
**[symptom 2]
**[symptom 3]
**[symptom 4]
**[symptom 5]
**[symptom 6]
*Symptoms of [disease name] may include the following:
:*

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T16:31:09Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T16:29:14Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome:
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome:
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of the individual diseases grouped together under Familial Hematuria & Hereditary Nephritis varies and is:
** Alport Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Thin Basement Membrane Disease: approximately [number or range] per 100,000 individuals worldwide.
** Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps: approximately [number or range] per 100,000 individuals worldwide.
** Pierson Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Epstein Syndrome: approximately [number or range] per 100,000 individuals worldwide.
** Fechtner Syndrome: approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T16:12:49Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, serologies).
:*Interstitial nephritis: Drugs, infectious agents, as well as autoimmune causes of interstitial nephritis
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T15:53:19Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, srologies).
:*Interstitial nephritis.
:*Pyelonephritis: Urine culture, and imaging studies to rule out structural abnormalities of the uro-genital tract which can predispose to reflux, obstruction, and recurrent infection should be performed and rules out.

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T15:49:07Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis and others. These are often accompanied by other clinical and laboratory findings (e.g. ESR, CRP, complement levels, srologies).
:*Interstitial nephritis.
:*Pyelonephritis XXXX

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-12T15:46:55Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS, e.g. autosomal recessive nephrotic syndrome of the Finnish type (NPHS1 mutation), podocin related autosomal recessive proteinuria/ESRD (NPHS2 mutation), autosomal dominant FSGS (α-actinine 4, ACTN4 mutation), and others. In genetic forms of FSGS, proteinuria is the hallmark, and hematuria mostly absent. Decline in renal function and endstage kidney disease is highly variable and based on the underlying genetic defect.
:*Inflammatory glomerular disorders, e.g. lupus nephritis, infection related glomerulonephritis,
:*Interstitial nephritis XXXX
:*Pyelonephritis XXXX

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T16:10:44Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria referenced here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*Genetic forms of FSGS (e.g. XXXX
:*Inflammatory glomerular disorders XXXX
:*Interstitial nephritis XXXX
:*Pyelonephritis XXXX

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T16:06:34Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria references here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testing.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T16:06:13Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria references here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins. Kidney biopsy can strenghte the clinical suspicion, however ultimate diagnosis is made through genetic testin.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T16:02:46Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria references here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characteristic findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strengthen the suspicion of a genetic defect in collagen IV, laminin, or myosin heavy chain biosynthesis, or cyteskeletal regulating proteins.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Physical Findings ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects (corneal and retinal defects, and anterior lenticonus), and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

:*

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T15:43:58Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating Familial Hematuria & Hereditary Nephritis from other Diseases==
*Familial Hematuria & Hereditary Nephritis refers to a mixed group of disorders which can significantly overlap with other categories of inherited glomerular kidney disorders (e.g. genetic forms of FSGS). While this differentiation is arbitrary and due to historical reasons, a clear distinction must be made between the familial forms of hematuria references here, and other causes of hematuria and kidney disease observered in infants, children, and adolescents:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-02-06T13:02:33Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153640)
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T22:07:15Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earlier in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T22:05:52Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
** Homozygous or compound heterozygous mutation in the LAMB2 gene on chromosome 3p21 (autosomal recessive) (OMIM # 609049)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T21:50:39Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
* Pierson Syndrome:
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
**This syndrome has been describe as a familial form of nephritis, associated with macrothrombocytopenia, renal failure, and hearing loss [PMID: 5011389]. Presentation resembles that of Alport Syndrome, and genetic testing may be required to distinguish these two disorders.
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T21:28:07Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].
*Thin Basement Membrane Disease:
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
*Nail-Patella Syndrome:
*Epstein Syndrome:
*Fechtner Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T21:23:36Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
**Heterozygous mutation in the MYH9 gene on chromosome 22q12 (autosomal dominant) (OMIM # 153650)
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].
*Nail-Patella Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T21:12:29Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. Other reports idnetified familial clustering of kidney disease in association with other abnormalities [PMID: 15416035]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome (also known as Onychoosteodysplasia, or Turner-Kieser syndrome, or Fong disease)
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
*Nail-Patella Syndrome
**Heterozygous mutation in the LIM-homeodomain protein LMX1B on the chromosome 9q33 (autosomal dominant) (OMIM #161200)
*Epstein Syndrome
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].
*Nail-Patella Syndrome:

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T21:01:03Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
*Nail-Patella Syndrome
*Epstein Syndrome
*Fechtner Syndrome
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T20:58:45Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a mixed group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria [link to hematuria chapter]. The prognosis and associate co-morbidities are highly variable and dependent on the underlying genetic disease. It can be benign as seen in 'Thin Basement-membrane Disease' or lead to early end stage kidney disease as seen in the X-linked form of Alport syndrome [reference].

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably and can be confusing. While the use of 'nephritis' in the term may imply inflammation, the disorders grouped here are NOT inflammatory in nature, nor due they reflect the involvement of a common pathway, inheritance pattern, or pathophysiology.

==Historical Perspective==
*A familial pattern of early childhood hematuria was first reported by Leonard G. Guthrie in 1902 [The Lancet, Volume 159, Issue 4105, 3 May 1902, Pages 1243–1246 Originally published as Volume 1, Issue 4105 - " IDIOPATHIC," OR CONGENITAL, HEREDITARY AND FAMILY HEMATURIA. LeonardG. Guthrie]. In the subsequent years, reports of early childhood hematuria, kidney failure (some associated to deafness or occular abnormalities), and early death in male offsprings emerged [PMID: 20773074] and [Hurst A.F., Guy's Hosp Rep. 73:368-370, 1923]. Initial reports of this familial pattern of hematuria, and kidney failure thought these presentations to be due to pyelonephritis. Later reports, based on kidney biopsies and autopsies, were proposing a glomerulonephritic process to be the primary cause [DOI: 10.1056/NEJM195910082611502]. The ever changing hypothesis of the underlying cause is perhaps a reflection of the various underlying disorders which were responsible in those families describe.

==Classification==
The following disorders are commonly grouped under the term 'Familial Hematuria and Hereditary Nephritis':
*Hereditary Disorders of Collagen Type IV:
**Thin Basement Membrane Disease (Benign Familial Hematuria)
**Alport Syndrome
**Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) (OMIM # 611773)
*Hereditary Disorders of Laminin:
**Pierson Syndrome
*Hereditary Disorder of basement membrane or cytoskletal gene regulation:
**Nail-Patella Syndrome
*Hereditary Disorders of cytoskeletal protein:
**Epstein Syndrome
**Fechtner Syndrome
It is arbitrary and due to historical reasons, why certain disease are commonly referenced in this category, while other forms of inherited kidney disorders of the glomerular filtration barrier are categorized elsewhere. At best, perhaps an early diagnosis of hematuria can be considered a common denominator, setting these disorders apart from most other forms of inherited kidney disorders.
==Causes==
*Alport syndrome can be due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070)
**Compund heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Homozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal recessive) (OMIM # 120070)
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
**X-linked mutations in the COL4A5 gene on the X-chromosome (X-linked dominant) (OMIM # 301050)
*Thin Basement Membrane Disease, also known as Thin Basement Membrane Nephropathy or Bening Familial Hematuria is due to:
**Heterozygous mutations in the COL4A3 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120070) or
**Heterozygous mutations in the COL4A4 gene on the chromosome 2q36 (autosomal dominant) (OMIM # 120131)
*Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC):
**Heterozygous mutations in the COL4A1 gene on the chromosome 13q34 (autosomal dominant) (OMIM # 611773)
**
==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name]

*

== Natural History, Complications and Prognosis==
*Alport Syndrome:
**The x-linked form of Alport Syndrome is more severe in males, leading to early end stage kidney disease between the ages 15-35 in the majority of affected individuals [PMID: 10752524]. By age 40 almost all male patients have developed end stage kidney disease. In contrary, only about less than one third of females will go to develop end stage kidney disease [PMID: 21071975]
**In females the x-linked form of Alport syndrome presents later in life, and is less severe [PMID: 14514738]. Nevertheless, end stage kidney disease can reach a prevalence of to 30% in this patient population.
**The autosomal recessive form of Alport syndrome is more severe and presents earielr in life than the autosomal dominat form [PMID: 21071975].

== Diagnosis ==
===Diagnostic Criteria===
*'Familial Hematuria' or 'Hereditary Nephritis' are clinical presentations rather than a diagnosis. A familial pattern of hematuria, proteinuria and kidney disease may raise the suspicion of a genetic disorder related to the above mentioned structural components of the glomerular filtration barrier (collagen type IV, laminin, cytoskeletal components). Characterisitc findings on a kidney biopsy (e.g. thinning and irregularities of the glomerular basement membrane), with or without ocular defects and hearing impairment may further strenghten the suspicion of a genetic defect in collagen IV biosynthesis.
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*The X-linked Alport syndrome in males as well as the autosomal recessive form of Alport syndrome are associated with ocular defects and hearing loss during childhood.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-24T20:41:08Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:23:51Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:18:03Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:15:26Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:10:03Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:08:59Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:05:54Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T19:02:51Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:36:26Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:19:03Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:16:11Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:10:12Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:09:27Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:06:31Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T17:00:14Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T16:01:03Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-13T15:44:22Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-12T22:31:04Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-12T22:19:14Z

Ali Poyan Mehr:

Familial Hematuria & Hereditary Nephritis

2017-01-12T21:37:06Z

Ali Poyan Mehr:

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

The term 'Familial Hematuria and Hereditary Nephritis' refers to a group of inherited kidney disorders which often present in early childhood and adolescence in form of microscopic hematuria (link to hematuria chapter). The prognosis is variable and based on the underlying disease and be benign or lead to early end stage kidney disease.

Unfortunately the term 'Familial Hematuria and Hereditary Nephritis' has been used variably, and some may consider incorrectly. This is due to the fact that the disorders referred to are not inflammatory as the name 'nephritisitis' may imply, but rahter due to genetic and structural defects of the glomerular filtration barrier.

==Historical Perspective==
*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

==Classification==
*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
:*[group1]
:*[group2]
:*[group3]
*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

==Causes==
* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* There are no established causes for [disease name].

==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Familial Hematuria & Hereditary Nephritis

2017-01-12T21:05:57Z

Ali Poyan Mehr: /* Overview */

__NOTOC__
{{SI}}
{{APM}}; {{AE}}

{{SK}} Synonym 1; Synonym 2; Synonym 3

==Overview==

Familial Hematuria and Hereditary Nephritis refers to a group of inherited kidney disorders which often present in early childhood and adolescence as microscopic hematuria (link to hematuria chapter) with preserved kidney function.
==Historical Perspective==
*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

==Classification==
*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
:*[group1]
:*[group2]
:*[group3]
*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

==Causes==
* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* There are no established causes for [disease name].

==Differentiating [disease name] from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[Differential dx1]
:*[Differential dx2]
:*[Differential dx3]

==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

===Age===
*Patients of all age groups may develop [disease name].

*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].

===Gender===
*[Disease name] affects men and women equally.

*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

===Race===
*There is no racial predilection for [disease name].

*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].

==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]

=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]

=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].

*A [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].

*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

== Treatment ==
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.

*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}