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Balkan endemic nephropathy

Marc E De Broe, MD, PhD
Section Editor
Gary C Curhan, MD, ScD
Deputy Editor
Alice M Sheridan, MD


Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with a high frequency of urothelial atypia, occasionally culminating in tumors of the renal pelvis and urethra.

Affected patients most commonly reside in southeastern Europe, including the areas traditionally considered to comprise the Balkans: Serbia, Bosnia and Herzegovina, Croatia, Romania, and Bulgaria. More specifically, BEN is most likely to occur among those living along the confluence of the Danube River, a region in which the plains and low hills generally have high humidity and rainfall. The most likely cause of BEN is exposure to aristolochic acid (AA). In contrast to the classic presentation of AA nephropathy, which is characterized by a rapid decline in renal function (six months to two years), BEN is slowly progressive (10 to 20 years), however, likely due to low-level exposure.

This topic reviews BEN. The classic presentation of AA nephropathy is discussed elsewhere. (See "Nephropathy induced by aristolochic acid (AA) containing herbs".)


The estimated prevalence of BEN in endemic areas ranges between 0.5 to 4.4 percent [1]. It has been suggested that the prevalence would be as high as 20 percent if aggressive screening were to be performed in at-risk populations; a striking observation is that nearly all affected patients were farmers. In some regions in Bosnia, approximately 10 percent of the patients on dialysis have BEN as the cause of end-stage renal disease (ESRD) [2].

Subsequent reports, however, suggest that the incidence of BEN is decreasing [3]. Since the early 1990s, the few new cases in one region in Serbia were only seen in previously affected families [4,5].


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Literature review current through: Sep 2016. | This topic last updated: Jun 22, 2015.
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