title: Pathophysiology of cisplatin-induced acute kidney injury.
abstract: Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado at Denver, P.O. Box C281, 12700 East 19th Avenue, Aurora, CO 80262, USA.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ozkok
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado at Denver, P.O. Box C281, 12700 East 19th Avenue, Aurora, CO 80262, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin