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Danubian endemic familial nephropathy (DEFN), also called Balkan endemic nephropathy, is a form of interstitial nephritis. 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 Croatiamarker, Bosnia and Herzegovinamarker, Serbiamarker, Romaniamarker and Bulgariamarker.

The first official publication was made by the Bulgarian nephrologist Dr.Yoto Tanchev and his team in 1956 in the Bulgarian Journal "Savremenna Medizina",9, 1956, 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 strange 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 anemia of hypochromous type, lack of proteinuria and slowly progression of the kidney failure. Tanchev et al. suggested this condition to be a disease sui generis. Their hypothesis for the etiology was related to a 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, an avalanche of research works and publications by Bulgarian and foreign scientists followed. Unfortunately, the etiology remains unknown till present. Dr. Yoto Tanchev died in the age of 83 in 2000.

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.


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 Jelaković, an associate professor at the Zagreb Universitymarker School of Medicine.

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