Nephrotoxicity induced by C- and N-arylsuccinimides

The succinimide ring is incorporated into hundreds of compounds that are widely used as agricultural, industrial, and pharmaceutical agents. Some succinimide derivatives that contain an aryl group on the ethylene bridge of the succinimide ring (C-arylsuccinimides) or on the nitrogen atom (N-arylsuccinimides) induce nephrotoxicity in humans and/or laboratory animals. Acute toxicity induced by this general class of compounds is typically characterized as polyuric renal failure, while chronic nephrotoxicity is seen as chronic interstitial nephritis. In this review, the structure-nephrotoxicity relationships, biotransformation, and mechanisms of nephrotoxicity for the C- and N-arylsuccinimides are examined.