Biotransformation enzymes in development of renal injury and urothelial cancer caused by aristolochic acid.

Ingestion of aristolochic acid (AA) is associated with the development of AA-nephropathy and Balkan endemic nephropathy, which are characterized by chronic renal failure, tubulointerstitial fibrosis, and urothelial cancer. Understanding which enzymes are involved in AA activation and/or detoxification is important in assessing susceptibility to AA. Xiao et al. demonstrate that hepatic cytochrome P450s in mice detoxicate AA and thereby protect kidney from injury. The relative contribution of enzymes activating AA to induce urothelial cancer in humans remains to be resolved.