Balkan endemic nephropathy and associated urothelial cancer.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease described only in some rural parts of southeastern Europe. One of its most peculiar characteristics is a strong association with upper urothelial cancer (UUC). BEN-related UUC has the same histological features as other forms of UUC in general, but is more frequently bilateral, less frequently affects the bladder and has a sex ratio close to 1. BEN and BEN-associated UUC share the same etiology. Over time, incidence of these conditions has been declining. Since BEN was first described, around half a century ago, socioeconomic changes (in housing, farming, living standards, etc.) have been profound and have obscured the factors responsible for the observed reduction in incidence. Whatever the causes of BEN, the disease might not be restricted only to southeastern Europe. Rather, the intensity of exposure to risk factors for BEN and, consequently, clustering of cases has more likely determined our knowledge of topographical distribution of an etiological entity that is much more widespread, or that might even be ubiquitous in its sporadic form.