title: Cisplatin nephrotoxicity: a review of the literature.
abstract: Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. It remains an important and effective therapy in many forms of cancer today. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Although it is best known for DNA damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic reticulum and mitochondria. It also activates apoptotic pathways and inflicts cellular damage via oxidative stress and inflammation. One of its dose limiting toxicities is its effects on the kidney. This includes acute kidney injury as well as tubular injury resulting in electrolyte wasting. Extensive research has found that cisplatin entry into a cell is facilitated by a number of cellular transporters including human copper transport protein 1 (Ctr1) and the organic cation transporter 2 (OCT2) which are expressed on renal tubular cells. The interactions between the mechanisms of cytotoxicity and cellular transport play an important role in the nephrotoxicity. Better understanding of these interactions could one day help devise better renoprotection that would not reduce its anti-tumor effects.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. Leung.nelson@mayo.edu.|Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. Leung.nelson@mayo.edu.
authors.forename: Nelson
authors.identifier: http://orcid.org/0000-0002-5651-1411
authors.initials: N
authors.lastname: Leung
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects* / Q000378:metabolism; D000079923:Copper Transporter 1; D004249:DNA Damage; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000075102:Organic Cation Transporter 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; C490079:SLC31A1 protein, human; D002945:Cisplatin
keywords: Chemotherapy; Cisplatin; Cytotoxicity; Nephrotoxicity; Renal protection