Newer Insights into Cisplatin Nephrotoxicity

Abstract

OBJECTIVE: To review recent advances in the understanding of the mechanisms of cisplatin nephrotoxicity. Factors affecting this toxicity and agents that may protect against it are discussed. DATA SOURCES: A MEDLINE search was used to identify pertinent literature including reviews. A manual search of bibliographies was performed to include all articles on the subject. STUDY SELECTION: All available data relating to the mechanisms, modifying factors, and management of cisplatin nephrotoxicity were assessed. DATA EXTRACTION: As limited human data are available, all animal studies were included. Articles with hypotheses or suggestions not backed by scientific data were excluded from review. DATA SYNTHESIS: Cisplatin is one of the most effective agents available for treating a variety of solid tumors. Nephrotoxicity is the dose-limiting factor for the use of this drug. Mechanisms for renal toxicity range from definitive histologic changes found in the proximal convoluted tubules to physiologic and biochemical alterations involving a decrease in mitochondrial respiratory function, enzymatic activity in the respiratory chain and glutathione peroxidase, and effects on cellular calcium homeostasis. Important factors related to nephrotoxicity include age, renal irradiation, and concurrent alcohol intake. Agents that appear promising in attenuating the nephrotoxic effects of cisplatin include loading with NaCl solution and/or mannitol, sodium thiosulfate, WR 2721, glutathione, probenecid, and many other compounds under active investigation. CONCLUSIONS: Cisplatin is a nephrotoxic drug; however, agents that may make cisplatin therapy more safe and rewarding will be available in the near future.