Cisplatin nephrotoxicity: a review.
BACKGROUND
Cisplatin is a major antineoplastic drug for the treatment of solid tumors, but it has dose-dependent renal toxicity.


METHODS
We reviewed clinical and experimental literature on cisplatin nephrotoxicity to identify new information on the mechanism of injury and potential approaches to prevention and/or treatment.


RESULTS
Unbound cisplatin is freely filtered at the glomerulus and taken up into renal tubular cells mainly by a transport-mediated process. The drug is at least partially metabolized into toxic species. Cisplatin has multiple intracellular effects, including regulating genes, causing direct cytotoxicity with reactive oxygen species, activating mitogen-activated protein kinases, inducing apoptosis, and stimulating inflammation and fibrogenesis. These events cause tubular damage and tubular dysfunction with sodium, potassium, and magnesium wasting. Most patients have a reversible decrease in glomerular filtration, but some have an irreversible decrease in glomerular filtration. Volume expansion and saline diuresis remain the most effective preventive strategies.


CONCLUSIONS
Understanding the mechanisms of injury has led to multiple approaches to prevention. Furthermore, the experimental approaches in these studies with cisplatin are potentially applicable to other drugs causing renal dysfunction.
Yao
Xin
X
Department of Internal Medicine, Texas Tech University Health Science Center, Lubbock, Texas 79430, USA.
Panichpisal
Kessarin
K
Kurtzman
Neil
N
Nugent
Kenneth
K
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control
D000970:Antineoplastic Agents; D002945:Cisplatin