Newer insights into cisplatin nephrotoxicity.
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.


METHODS
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.


METHODS
All available data relating to the mechanisms, modifying factors, and management of cisplatin nephrotoxicity were assessed.


METHODS
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.


RESULTS
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.
Anand
A J
AJ
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Bashey
B
B
D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D005665:Furosemide / Q000627:therapeutic use; D005978:Glutathione / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D012965:Sodium Chloride / Q000627:therapeutic use; D013885:Thiosulfates / Q000627:therapeutic use
D013885:Thiosulfates; D008353:Mannitol; D012965:Sodium Chloride; D005665:Furosemide; D005978:Glutathione; C017717:sodium thiosulfate; D004999:Amifostine; D002945:Cisplatin