A historical overview of Balkan Endemic Nephropathy (BEN) in relation to published hypotheses.

Balkan Endemic Nephropathy occurs with a high rate of prevalence in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. The first cases described in Bulgaria, Serbia and Romania date to the late 1950s and early 1960s. BEN has been characterized to date as a chronic, slowly progressive familial tubular interstitial renal disease of unknown aetiology. The disease is characterized by its endemic nature, long incubation period, the familial clustering of the disease, and a exceptionally high incidence of upper urothelial tumour associated with BEN. To date several hypotheses have presented some findings that could be relevant to the etiology of BEN, but only one of them, chronic poisoning with Aristolochic acids, has provided convincing evidence related to BEN etiology and its clinical characteristics.