Cisplatin nephrotoxicity: insights into mechanism

Cis-dichlorodiammine platinum (II), or cisplatin, is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity. Acute and chronic nephrotoxicity of cisplatin occurs in man and animals especially after repeated administration. Morphological damage is restricted to the P3 segment of the proximal tubule. Abnormalities of water and solute reclamation and transglomerular passage of fluid are commonly associated with cisplatin nephrotoxicity. The vulnerability of the kidney to cisplatin may be related to its function as the primary excretory organ for platinum. Platinum binds to multiple cellular organelles and macromolecules, yet the precise mechanism of its cytotoxicity has not been delineated. Because abnormalities in renal function are preceded by a period where gross renal function appears normal, it is an ideal model to study the early physiological and biochemical determinants of metal induced acute renal failure.