Balkan nephropathy
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, a priority generally acknowledged by the international nephrological community. 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
-  may be classified according to  into  subtypes/groups:
- Other variants of  include , , and .

# Pathophysiology
- The etiology for Balkan nephropathy is currently unknown..
- 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.

# Causes
The etiology for DEFN is currently unknown..  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. 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 Jelakovic, an associate professor at the Zagreb University School of Medicine. 

# Clinical Features

# Differentiating  from other Diseases
-  must be differentiated from other diseases that cause , , and , such as:

# Epidemiology and Demographics
- The prevalence of  is approximately  per 100,000 individuals worldwide.
- In , the incidence of  was estimated to be  cases per 100,000 individuals in .

## Age
- Patients of all age groups may develop .
-  is more commonly observed among patients aged  years old.
-  is more commonly observed among .

## Gender
-  affects men and women equally.
-  are more commonly affected with  than .
- The  to  ratio is approximately  to 1.

## Race
- There is no racial predilection for .
-  usually affects individuals of the  race.
-  individuals are less likely to develop .

# Risk Factors
- Common risk factors in the development of  are , , , and .

# Natural History, Complications and Prognosis
- The majority of patients with  remain asymptomatic for .
- Early clinical features include , , and .
- If left untreated,  of patients with  may progress to develop , , and .
- Common complications of  include , , and .
- Prognosis is generally , and the  of patients with  is approximately .

# Diagnosis

## Diagnostic Criteria
- The diagnosis of  is made when at least  of the following  diagnostic criteria are met:

## Symptoms
-  is usually asymptomatic.
- Symptoms of  may include the following:

## Physical Examination
- Patients with  usually appear .
- Physical examination may be remarkable for:

## Laboratory Findings
- There are no specific laboratory findings associated with .
- A    is diagnostic of .
- An  concentration of   is diagnostic of .
- Other laboratory findings consistent with the diagnosis of  include , , and .

## Imaging Findings
- There are no  findings associated with .
-  is the imaging modality of choice for .
- On ,  is characterized by , , and .
-  may demonstrate , , and .

## Other Diagnostic Studies
-  may also be diagnosed using .
- Findings on  include , , and .

# Treatment

## Medical Therapy
- There is no treatment for ; the mainstay of therapy is supportive care.
- The mainstay of therapy for  is  and .
-  acts by .
- Response to  can be monitored with  every .

## Surgery
- Surgery is the mainstay of therapy for .
-  in conjunction with  is the most common approach to the treatment of .
-  can only be performed for patients with  .

## Prevention
- There are no primary preventive measures available for .
- Effective measures for the primary prevention of  include , , and .
- Once diagnosed and successfully treated, patients with  are followed-up every . Follow-up testing includes , , and .