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| __NOTOC__
| | ===Pathogenesis=== |
| {{Focal segmental glomerulosclerosis}} | | *Transmission to the [[fetus]] is [[transplacental]], it can also occur during [[delivery]] in the presence of maternal genital lesions.<ref name="pmid11438902">{{cite journal| author=Wicher V, Wicher K| title=Pathogenesis of maternal-fetal syphilis revisited. | journal=Clin Infect Dis | year= 2001 | volume= 33 | issue= 3 | pages= 354-63 | pmid=11438902 | doi=10.1086/321904 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11438902 }} </ref><ref name="pmid27333146">{{cite journal| author=Domingues RM, Leal Mdo C| title=[Incidence of congenital syphilis and factors associated with vertical transmission: data from the Birth in Brazil study]. | journal=Cad Saude Publica | year= 2016 | volume= 32 | issue= 6 | pages= | pmid=27333146 | doi=10.1590/0102-311X00082415 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27333146 }} </ref><ref name="pmid16362988">{{cite journal| author=Peeling RW, Hook EW| title=The pathogenesis of syphilis: the Great Mimicker, revisited. | journal=J Pathol | year= 2006 | volume= 208 | issue= 2 | pages= 224-32 | pmid=16362988 | doi=10.1002/path.1903 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16362988 }} </ref> |
| {{CMG}};{{APM}}; '''Associate Editor-In-Chief:’’’ {{CZ}}; {{OO}} | | *The risk of transmission to the fetus is dependent on the stage of the maternal disease(dependent on the spirochete concentration in the blood stream) and the duration of exposure to the fetus in utero.<ref name="pmid15356936">{{cite journal| author=Berman SM| title=Maternal syphilis: pathophysiology and treatment. | journal=Bull World Health Organ | year= 2004 | volume= 82 | issue= 6 | pages= 433-8 | pmid=15356936 | doi= | pmc=2622860 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15356936 }} </ref> |
| | *The risk of vertical transmission of syphilis from an infected untreated mother decreases as maternal disease duration progresses: transmission risk of 70–100% for primary syphilis and 40% for early latent syphilis to 10% for late latent disease. The variation in the percentages with the duration of infection is because the concentration of spirochetes in the blood stream decrease with the duration of maternal syphilis infection.<ref name="pmid10858706">{{cite journal |vauthors=Genç M, Ledger WJ |title=Syphilis in pregnancy |journal=Sex Transm Infect |volume=76 |issue=2 |pages=73–9 |year=2000 |pmid=10858706 |pmc=1758294 |doi= |url=}}</ref> |
| | *Kassowitz's law describes the an inverse relationship of interval between the disease and pregnancy. Longer the interval between infection and pregnancy more benign is the outcome.<ref name="pmid23919053">{{cite journal| author=Balaji G, Kalaivani S| title=Observance of Kassowitz law-late congenital syphilis: Palatal perforation and saddle nose deformity as presenting features. | journal=Indian J Sex Transm Dis | year= 2013 | volume= 34 | issue= 1 | pages= 35-7 | pmid=23919053 | doi=10.4103/0253-7184.112869 | pmc=3730472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23919053 }} </ref> |
| | *Transmission of infection typically takes place between the 16th and 28th week of pregnancy, however the transmission can be as early as the first trimester of pregnancy.<ref name="pmid56895">{{cite journal |vauthors=Harter C, Benirschke K |title=Fetal syphilis in the first trimester |journal=Am. J. Obstet. Gynecol. |volume=124 |issue=7 |pages=705–11 |year=1976 |pmid=56895 |doi= |url=}}</ref |
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| ==Overview== | | ===Microscopic Pathology=== |
| | *Skin lesion on histopahological exam demonstrate perivascular infiltration by lymphocytes, plasma cells and histiocytes, with endarteritis and extensive fibrosis. |
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| ==Pathophysiology== | | ==Risk Factors== |
| The underlying pathogenesis of FSGS clinical signs and symptoms is fusion or effacement of the foot processes ([[podocytes]]) of the [[glomeruli]], with sclerosing of some part of the [[glomeruli]] (hence its name as focal segmental). FSGS is believed to a histological variant of Minimal Change Kidney Disease rather than a clinical disease by itself.
| | Risk factors for congenital syphilis include all the risk factors which predispose a pregnant woman to have syphilis infection:<nowiki><ref name="pmid2356911">{{cite journal| author=Rolfs RT, Goldberg M, Sharrar RG| title=Risk factors for syphilis: cocaine use and prostitution. | journal=Am J Public Health | year= 1990 | volume= 80 | issue= 7 | pages= 853-7 | pmid=2356911 | doi= | pmc=1404975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2356911 }} </ref></nowiki><nowiki><ref name="pmid17675391">{{cite journal| author=Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM et al.| title=Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China. | journal=Sex Transm Infect | year= 2007 | volume= 83 | issue= 6 | pages= 476-80 | pmid=17675391 | doi=10.1136/sti.2007.026187 | pmc=2598725 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17675391 }} </ref></nowiki><nowiki><ref name="pmid15247352">{{cite journal| author=Hook EW, Peeling RW| title=Syphilis control--a continuing challenge. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 2 | pages= 122-4 | pmid=15247352 | doi=10.1056/NEJMp048126 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15247352 }} </ref></nowiki><nowiki><ref name="pmid16205297">{{cite journal| author=Buchacz K, Greenberg A, Onorato I, Janssen R| title=Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention. | journal=Sex Transm Dis | year= 2005 | volume= 32 | issue= 10 Suppl | pages= S73-9 | pmid=16205297 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16205297 }} </ref></nowiki><nowiki><ref name="pmid25514173">{{cite journal| author=Solomon MM, Mayer KH| title=Evolution of the syphilis epidemic among men who have sex with men. | journal=Sex Health | year= 2015 | volume= 12 | issue= 2 | pages= 96-102 | pmid=25514173 | doi=10.1071/SH14173 | pmc=4470884 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25514173 }} </ref></nowiki><nowiki><ref name="pmid24927712">{{cite journal| author=Hakre S, Arteaga GB, Núñez AE, Arambu N, Aumakhan B, Liu M et al.| title=Prevalence of HIV, syphilis, and other sexually transmitted infections among MSM from three cities in Panama. | journal=J Urban Health | year= 2014 | volume= 91 | issue= 4 | pages= 793-808 | pmid=24927712 | doi=10.1007/s11524-014-9885-4 | pmc=4134449 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24927712 }} </ref></nowiki><nowiki><ref name="newell">Newell, J., et al. "A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour." Genitourinary medicine 69.6 (1993): 421-426.</ref></nowiki> |
| The clinical hallmark of focal segmental glomerulosclerosis (FSGS) is [[proteinuria]] and [[nephrotic syndrome]]. As such, the involvement of the permselective filtration barrier and effacement of podocyte foot processes are inevitable.<ref name="pmid14712353">{{cite journal| author=Asanuma K, Mundel P| title=The role of podocytes in glomerular pathobiology. | journal=Clin Exp Nephrol | year= 2003 | volume= 7 | issue= 4 | pages= 255-9 | pmid=14712353 | doi=10.1007/s10157-003-0259-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14712353 }} </ref>
| | *Inadequate antenatal care |
| According to Asanuma and colleagues,<ref name="pmid14712353">{{cite journal| author=Asanuma K, Mundel P| title=The role of podocytes in glomerular pathobiology. | journal=Clin Exp Nephrol | year= 2003 | volume= 7 | issue= 4 | pages= 255-9 | pmid=14712353 | doi=10.1007/s10157-003-0259-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14712353 }} </ref> 4 major causes that lead to the reaction of podocyte foot processes. These changes result in [[apoptosis]], detachment from the glomerular basement membrane (GBM), and subsequent podocytopenia:<ref name="pmid12704576"></ref>
| | *Multiple sexual partners |
| #Interference with slit diaphragm and its corresponding [[lipid raft]]
| | *Prostitution |
| #Interference with [[actin]] cytoskeleton
| | *Illicit drug use |
| #Interference with the [[glomerular basement membrane|GBM]] or with the interaction of the [[glomerular basement membrane|GBM]] and the [[podocytes]]
| | *Unprotected sex |
| #Interference with the negative charge of [[podocytes]]
| | *Residence in highly prevalent areas |
| | | *[[Human Immunodeficiency Virus (HIV)|HIV]] infection |
| The pathogenesis of Primary or Idiopathic FSGS is not so clear. Many studies had theorized that FSGS occurs as a consequence of effects of circulating immune activating factors on the glomerular epithelium. Indeed, the damaging role of circulating factors like the soluble urokinase plasminogen activating receptor (suPAR) on the glomerular podocytes had been postulated.<ref name="pmidPMID 25168830">{{cite journal| author=Reiser J, Nast CC, Alachkar N| title=Permeability factors in focal and segmental glomerulosclerosis. | journal=Adv Chronic Kidney Dis | year= 2014 | volume= 21 | issue= 5 | pages= 417-21 | pmid=PMID 25168830 | doi=10.1053/j.ackd.2014.05.010 | pmc=4149759 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25168830 }} </ref> However, there are not enough clinical data to support this pathogenic theory probably because of the several other physiologic forms of suPAR that can be identified by [[ELISA]].<ref name="pmid23138488">{{cite journal| author=Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ et al.| title=Circulating suPAR in two cohorts of primary FSGS. | journal=J Am Soc Nephrol | year= 2012 | volume= 23 | issue= 12 | pages= 2051-9 | pmid=23138488 | doi=10.1681/ASN.2012030302 | pmc=3507361 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23138488 }} </ref>
| | *Presence of other [[STI]]<nowiki/>s |
| ===Role of "Circulating Permeability Factor"===
| | *Previous history of STIs |
| The initial insult that causes effacement of foot processes is yet to be discovered. Circulating factors implicated in the [[pathogenesis]] of Primary FSGS include the Soluble Urokinase Plasminogen Activating Receptor (suPAR) and [[MicroRNAs]]. [[MicroRNAs]] are small endogenous (18 to 24 [[nucleotides]] long) noncoding single-stranded RNAs that regulate [[gene expression]] at the post-transcriptional level. Specifically, [[microRNAs]] bind to the messenger RNAs of various genes and lead to their breakdown. <ref name="pmidPMID 25168830">{{cite journal| author=Reiser J, Nast CC, Alachkar N| title=Permeability factors in focal and segmental glomerulosclerosis. | journal=Adv Chronic Kidney Dis | year= 2014 | volume= 21 | issue= 5 | pages= 417-21 | pmid=PMID 25168830 | doi=10.1053/j.ackd.2014.05.010 | pmc=4149759 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25168830 }} </ref>Expression of a specific microRNA called miR-193a produced FSGS in mice but its implication in human podocytopathy has not been clearly defined.
| | *Intravenous drug use |
| | | *Health care professionals who are predisposed to occupational risk |
| suPAR is a heavily glycosylated protein that can be found in several places. It can be present as different fragments and also with various degrees of glycosylation. Both fragmentation and glycosylation of suPAR determine its function and the way it is measured (mainly by ELISA). The most pathogenic form of suPAR for podocytes is still not well defined but there are laboratory evidences of suPAR causing FSGS in lab mice<ref name="pmid23138488">{{cite journal| author=Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ et al.| title=Circulating suPAR in two cohorts of primary FSGS. | journal=J Am Soc Nephrol | year= 2012 | volume= 23 | issue= 12 | pages= 2051-9 | pmid=23138488 | doi=10.1681/ASN.2012030302 | pmc=3507361 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23138488 }} </ref> and several cohort studies linking high level of suPAR to FSGS.<ref name="pmid23447064">{{cite journal| author=Huang J, Liu G, Zhang YM, Cui Z, Wang F, Liu XJ et al.| title=Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis. | journal=Kidney Int | year= 2013 | volume= 84 | issue= 2 | pages= 366-72 | pmid=23447064 | doi=10.1038/ki.2013.55 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23447064 }} </ref>
| | *Low socioeconomic status |
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| Nonetheless, Shalhoub and colleagues hypothesized in 1974 the involvement of "circulating permeability factor."<ref name="pmid4140273">{{cite journal| author=Shalhoub RJ| title=Pathogenesis of lipoid nephrosis: a disorder of T-cell function. | journal=Lancet | year= 1974 | volume= 2 | issue= 7880 | pages= 556-60 | pmid=4140273 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4140273 }} </ref> In fact, several elements favor the pathological role of "circulating permeability factor" in FSGS:
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| *Recurrence of [[proteinuria]] following [[renal transplantation]]<ref name="pmid1994534">{{cite journal| author=Ingulli E, Tejani A| title=Incidence, treatment, and outcome of recurrent focal segmental glomerulosclerosis posttransplantation in 42 allografts in children--a single-center experience. | journal=Transplantation | year= 1991 | volume= 51 | issue= 2 | pages= 401-5 | pmid=1994534 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1994534 }} </ref>
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| *Absence of [[proteinuria]] in patients following [[renal transplantation|transplantation]] in recipients of kidneys from donors with FSGS<ref name="pmid11158426">{{cite journal| author=Rea R, Smith C, Sandhu K, Kwan J, Tomson C| title=Successful transplant of a kidney with focal segmental glomerulosclerosis. | journal=Nephrol Dial Transplant | year= 2001 | volume= 16 | issue= 2 | pages= 416-7 | pmid=11158426 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11158426 }} </ref>
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| *Effectiveness of extracorporeal [[plasmapheresis]] in decreasing the degree of [[proteinuria]]<ref name="pmid11328888">{{cite journal| author=Ghiggeri GM, Artero M, Carraro M, Perfumo F| title=Permeability plasma factors in nephrotic syndrome: more than one factor, more than one inhibitor. | journal=Nephrol Dial Transplant | year= 2001 | volume= 16 | issue= 5 | pages= 882-5 | pmid=11328888 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11328888 }} </ref>
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| *''In vitro'' studies showing permeability alterations by FSGS serum on isolated [[glomeruli]]<ref name="pmid12704575">{{cite journal| author=Savin VJ, McCarthy ET, Sharma M| title=Permeability factors in focal segmental glomerulosclerosis. | journal=Semin Nephrol | year= 2003 | volume= 23 | issue= 2 | pages= 147-60 | pmid=12704575 | doi=10.1053/snep.2003.50024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12704575 }} </ref>
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| *Transmissibility of glomerular permeability factor from the mother to her infant during [[gestation]]<ref name="pmid11195803">{{cite journal| author=Kemper MJ, Wolf G, Müller-Wiefel DE| title=Transmission of glomerular permeability factor from a mother to her child. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 5 | pages= 386-7 | pmid=11195803 | doi=10.1056/NEJM200102013440517 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11195803 }} </ref>
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| ===Role of Proteinuria===
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| [[Proteinuria]], an important predictor of prognosis, further exacerbates [[renal disease]] by inducing [[tubulointerstitial diseases of the kidney|tubulointerstitial injury]]. [[Proteinuria]] induces the activation of [[immune cells]], such as [[macrophages]] and [[T-cells]], and [[cytokines]], such as tumor growth factor-beta ([[TGF-beta]]), [[interleukin 1|interleukin (IL) 1]], and tumor necrosis factor-alpha ([[TNF-alpha]]).<ref name="pmid11158854">{{cite journal| author=Walls J| title=Relationship between proteinuria and progressive renal disease. | journal=Am J Kidney Dis | year= 2001 | volume= 37 | issue= 1 Suppl 2 | pages= S13-6 | pmid=11158854 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11158854 }} </ref>
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| ===Role of Inflammatory Mediators===
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| The progression of FSGS is highly dependent on the presence of pro-inflammatory cytokines and vasoactive factors that also play a major role in renal fibrosis. Overexpression of tumor growth factor-beta ([[TGF-beta]]), [[platelet-derived growth factor]] (PDGF), and [[vascular endothelial growth factor]] (VEGF) contributes to the progression of disease and is associated with the extent of [[glomerulosclerosis]].<ref name="pmid11423572">{{cite journal| author=Kang DH, Joly AH, Oh SW, Hugo C, Kerjaschki D, Gordon KL et al.| title=Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. | journal=J Am Soc Nephrol | year= 2001 | volume= 12 | issue= 7 | pages= 1434-47 | pmid=11423572 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11423572 }} </ref><ref name="pmid16409155">{{cite journal| author=Harris RC, Neilson EG| title=Toward a unified theory of renal progression. | journal=Annu Rev Med | year= 2006 | volume= 57 | issue= | pages= 365-80 | pmid=16409155 | doi=10.1146/annurev.med.57.121304.131342 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16409155 }} </ref> Activated [[cytokines]] promote cellular infiltration and desposition of [[collagen]] along the mesangial matrix.<ref name="pmid16409155">{{cite journal| author=Harris RC, Neilson EG| title=Toward a unified theory of renal progression. | journal=Annu Rev Med | year= 2006 | volume= 57 | issue= | pages= 365-80 | pmid=16409155 | doi=10.1146/annurev.med.57.121304.131342 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16409155 }} </ref>
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| ===Maladaptive Interactions===
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| Following the loss of [[podocytes]], maladaptive interactions occur between the [[glomerular basement membrane|GBM]] and the renal epithelial cells, leading to proliferation of epithelial, endothelial, and mesangial cells.<ref name="pmid12704576">{{cite journal| author=Fogo AB| title=Animal models of FSGS: lessons for pathogenesis and treatment. | journal=Semin Nephrol | year= 2003 | volume= 23 | issue= 2 | pages= 161-71 | pmid=12704576 | doi=10.1053/snep.2003.50015 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12704576 }}</ref> The resultant collagen deposition then contributes to the scarring of the glomerular tufts that appear as focal and segmental regions of glomerulosclerosis as seen on pathology. The diseased regions then progress to involve larger areas of the kidneys and eventually become diffusely sclerotic, causing end-stage renal disease (ESRD).<ref name="pmid12704576"></ref>
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| ===Role of Mechanical Stresses===
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| Defects of the [[glomerular filtration]] barrier leads to an overwhelmingly increased single nephron [[glomerular filtration rate]] (SNGFR). This [[mechanical stress]] helps in the progression of FSGS by creating a state of hypertrophy that worsens the lack of balance between the GBM and the podocytopenia, and thus worsens the extent of injury.<ref name="pmid18039119">{{cite journal| author=Kwoh C, Shannon MB, Miner JH, Shaw A| title=Pathogenesis of nonimmune glomerulopathies. | journal=Annu Rev Pathol | year= 2006 | volume= 1 | issue= | pages= 349-74 | pmid=18039119 | doi=10.1146/annurev.pathol.1.110304.100119 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18039119 }} </ref><ref name="pmid12704579">{{cite journal| author=Hostetter TH| title=Hyperfiltration and glomerulosclerosis. | journal=Semin Nephrol | year= 2003 | volume= 23 | issue= 2 | pages= 194-9 | pmid=12704579 | doi=10.1053/anep.2003.50017 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12704579 }} </ref>
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| ===Role of Genetics===
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| There are currently several mutations in cytoskeletal and membrane proteins that lead to familial FSGS:
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| *''Nephrin'' gene in congenital Finnish-type nephrotic syndrome - ''NPHS1''<ref name="pmid9660941">{{cite journal| author=Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H et al.| title=Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. | journal=Mol Cell | year= 1998 | volume= 1 | issue= 4 | pages= 575-82 | pmid=9660941 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9660941 }} </ref><ref name="pmid18039119">{{cite journal| author=Kwoh C, Shannon MB, Miner JH, Shaw A| title=Pathogenesis of nonimmune glomerulopathies. | journal=Annu Rev Pathol | year= 2006 | volume= 1 | issue= | pages= 349-74 | pmid=18039119 | doi=10.1146/annurev.pathol.1.110304.100119 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18039119 }} </ref>
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| *''Nephrin-like transmembrane'' gene - ''NEPH1''<ref name="pmid14712353">{{cite journal| author=Asanuma K, Mundel P| title=The role of podocytes in glomerular pathobiology. | journal=Clin Exp Nephrol | year= 2003 | volume= 7 | issue= 4 | pages= 255-9 | pmid=14712353 | doi=10.1007/s10157-003-0259-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14712353 }} </ref>
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| *''Podocin'' gene - ''NPHS2''<ref name="pmid16571882">{{cite journal| author=Tryggvason K, Patrakka J, Wartiovaara J| title=Hereditary proteinuria syndromes and mechanisms of proteinuria. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 13 | pages= 1387-401 | pmid=16571882 | doi=10.1056/NEJMra052131 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16571882 }} </ref>
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| *CD2-associated protein (CD2AP)<ref name="pmid10514378">{{cite journal| author=Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O et al.| title=Congenital nephrotic syndrome in mice lacking CD2-associated protein. | journal=Science | year= 1999 | volume= 286 | issue= 5438 | pages= 312-5 | pmid=10514378 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10514378 }} </ref><ref name="pmid12764198">{{cite journal| author=Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH et al.| title=CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. | journal=Science | year= 2003 | volume= 300 | issue= 5623 | pages= 1298-300 | pmid=12764198 | doi=10.1126/science.1081068 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12764198 }} </ref>
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| *''Alpha-actinin-4'' gene <ref name="pmid10700177">{{cite journal| author=Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ et al.| title=Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. | journal=Nat Genet | year= 2000 | volume= 24 | issue= 3 | pages= 251-6 | pmid=10700177 | doi=10.1038/73456 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10700177 }} </ref>
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| *Transient receptor potential cation channel - TRPC6<ref name="pmid12953036">{{cite journal| author=Winn MP| title=Approach to the evaluation of heritable diseases and update on familial focal segmental glomerulosclerosis. | journal=Nephrol Dial Transplant | year= 2003 | volume= 18 Suppl 6 | issue= | pages= vi14-20 | pmid=12953036 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12953036 }} </ref>
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| *Mutation in ''wilms tumor'' gene - ''WT1''<ref name="pmid23871408">{{cite journal| author=Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH et al.| title=KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. | journal=Am J Kidney Dis | year= 2013 | volume= 62 | issue= 3 | pages= 403-41 | pmid=23871408 | doi=10.1053/j.ajkd.2013.06.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871408 }} </ref>
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| *Mutation in ''SCARB2 (LIMP2)'' gene<ref name="pmid23871408">{{cite journal| author=Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH et al.| title=KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. | journal=Am J Kidney Dis | year= 2013 | volume= 62 | issue= 3 | pages= 403-41 | pmid=23871408 | doi=10.1053/j.ajkd.2013.06.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871408 }} </ref>
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| *Mutation in ''formin'' gene - ''INF2''<ref name="pmid23871408">{{cite journal| author=Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH et al.| title=KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. | journal=Am J Kidney Dis | year= 2013 | volume= 62 | issue= 3 | pages= 403-41 | pmid=23871408 | doi=10.1053/j.ajkd.2013.06.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871408 }} </ref>
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| *Mitochondrial cytopathies<ref name="pmid23871408">{{cite journal| author=Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH et al.| title=KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. | journal=Am J Kidney Dis | year= 2013 | volume= 62 | issue= 3 | pages= 403-41 | pmid=23871408 | doi=10.1053/j.ajkd.2013.06.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871408 }} </ref>
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| ==References==
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| {{Reflist|2}}
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| {{WH}}
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| {{WS}}
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