A molecular basis for target-cell toxicity and upper urothelial carcinoma in analgesic abusers and patients with Balkan endemic nephropathy.

Ochratoxin A is ubiquitous in regions where Balkan endemic nephropathy is common. It damages the kidney cortex in a range of experimental animals and induces renal parenchymal carcinoma in mice, but it is not a potent carcinogen, nor is there experimental evidence to link it to upper urothelial carcinoma (UUC). A model UUC can be induced experimentally in rodents by urothelial initiation, followed by an acutely induced papillary necrosis. This two-stage experimental model may help to clarify the role of ochratoxin A in initiating or promoting upper urothelial cells and increase our understanding of the development of UUC in patients with Balkan endemic nephropathy.