Role of Environmental Toxins in Endemic (Balkan) Nephropathy

An international symposium, held in Zagreb, Croatia, in October 2006, brought together basic scientists and clinical investigators engaged in research on endemic (Balkan) nephropathy, a chronic renal tubulointerstitial disease of previously unknown cause that often is accompanied by upper urinary tract urothelial cancer. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, a similar clinical entity occurs throughout Europe, Asia, and North America. Recent advances in the understanding of endemic nephropathy now favor the causative role of aristolochic acid over the ubiquitous mycotoxin known as ochratoxin A. Specifically, aristolactam-DNA adducts have been found in renal tissues and urothelial cancers of affected patients. A "signature" p53 mutation in the upper urothelial cancer associated with this disease provides evidence of long-term exposure to aristolochic acid. In addition, the renal pathophysiology and histopathology observed in endemic nephropathy most closely resemble the entity known as aristolochic acid nephropathy. Public health authorities in countries harboring this disease are encouraged to reduce the potential for dietary exposure to Aristolochia clematitis.