title: An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity.
abstract: Cisplatin is among the most effective chemotherapeutic agents against solid tumors. Nephrotoxicity is the most common side effect of cisplatin chemotherapy, which limits the clinical use of cisplatin and seriously worsens the quality of life of cancer patients resulting in dosage reduction and discontinuation of treatment. Cisplatin involves a complex multifactorial process, as it has direct toxic effect on cells of the renal tubules, vasculature and glomeruli, and causes alterations in renal blood flow and glomerular filtration rate. Indirectly, cisplatin also induces inflammation of the renal interstitium, which contributes to the acute damage and may lead to chronic interstitial fibrosis, indicative of irreversible renal damage. This review presents an integrative view of the pathophysiological effects of cisplatin on tubular, vascular, glomerular, and interstitial function and the interplay among these actions. Moreover, it reviewed human clinical trials of the last ten years in order to evaluate the incidence and severity of the renal injury induced by cisplatin at the doses and therapeutic guidelines used in the clinical practice.
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
authors.forename: Penélope D
authors.initials: PD
authors.lastname: Sánchez-González
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernández
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
authors.forename: Ana I
authors.initials: AI
authors.lastname: Morales
mesh_terms: D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D002908:Chronic Disease; D002945:Cisplatin / Q000009:adverse effects* / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000503:physiopathology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin