Balkan nephropathy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2] Aarti Narayan, M.B.B.S [3]

Synonyms and keywords: Danubian endemic familial nephropathy; DEFN; Balkan endemic nephropathy; BEN; Nephropathica endemica

Overview

Balkan nephropathy is a form of chronic interstitial nephritis that is endemic to limited areas of Bulgaria, the former Yugoslavia, and Romania. It is characterized by a progressive shrinking of the kidneys that is often associated with uroepithelial tumors. It was first identified in the 1920s among several small, discrete communities along the Danube River and its major tributaries, in the modern countries of Croatia, Bosnia, Serbia, Romania and Bulgaria. A striking feature of the disease is its very localized occurrence. There are approximately ten small areas where it occurs, all of them more or less rural, but nothing seems to connect those areas other than the occurrence of this illness.

Historical Perspective

The first official publication was made by the Bulgarian nephrologist Dr. Yoto Tanchev and his team in 1956 in the Bulgarian Journal Savremenna Medizina,[2] a priority generally acknowledged by the international nephrological community.[3] Their study was based on a wide screening of inhabitants of the villages around the town of Vratsa, Bulgaria. Their contribution to the study of this unusual endemic disease of the kidneys consisted in the description of symptoms which were not typical for the common chronic nephritis, i.e., incidence only in adults (no children affected), lack of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, a lack of proteinuria, and slow progression to chronic kidney failure.

A striking feature of the disease is its very localized occurrence. There are approximately ten small areas where it occurs, all of them more or less rural, but nothing seems to connect those areas, other than the occurrence of this illness. Tanchev and colleagues suggested the condition was a disease sui generis. Their initial hypothesis for the etiology was possible intoxication with heavy metals, because the villages affected were supplied with water coming from the nearby karst-type Vratsa Mountain.

The first name of the disease was "Vratsa nephritis". Later, following descriptions of similar ailments in Yugoslavia and Romania, the condition became known as Balkan endemic nephropathy.

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 etiology for Balkan nephropathy is currently unknown.[1].
  • It has recently been hypothesized that chronic exposure to dietary aristolochic acid is a major risk for Balkan nephropathy. *Aristolochic acid may come from Aristolochia clematitis, a plant native to the endemic region, and its seeds may comingle with wheat used for bread.[2]

Causes

The etiology for DEFN is currently unknown.[3]. It has recently been hypothesized that chronic exposure to dietary aristolochic acid is a major risk for DEFN. Aristolochic acid may come from Aristolochia clematitis, a plant native to the endemic region, and its seeds may comingle with wheat used for bread.[4] This theory has recently gained further support through research by Arthur P. Grollman, cancer biologist and the director of Stony Brook University's chemical biology lab in New York, and Bojan Jelaković, an associate professor at the Zagreb University School of Medicine. [5]

Clinical Features

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

  1. Batuman V (2006). "Fifty years of Balkan endemic nephropathy: daunting questions, elusive answers". Kidney Int. 69 (4): 644–6. doi:10.1038/sj.ki.5000231. PMID 16467889.
  2. Grollman AP, Shibutani S, Moriya M; et al. (2007). "Aristolochic acid and the etiology of endemic (Balkan) nephropathy". doi:10.1073/pnas.0701248104. PMID 17620607.
  3. Batuman V (2006). "Fifty years of Balkan endemic nephropathy: daunting questions, elusive answers". Kidney Int. 69 (4): 644–6. doi:10.1038/sj.ki.5000231. PMID 16467889.
  4. Grollman AP, Shibutani S, Moriya M; et al. (2007). "Aristolochic acid and the etiology of endemic (Balkan) nephropathy". Proc. Natl. Acad. Sci. U.S.A. 104 (29): 12129–34. doi:10.1073/pnas.0701248104. PMID 17620607.
  5. Julia C. Mead (2007). "Manna from hell". The Scientist. 21 (11): 44.

Related Chapters

References



hr:Balkanska endemska nefropatija


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