Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection

• Published in: PloS one 2014-07, Vol.9 (7), p.e101902
• Main Authors: Kidera, Yasuhiro, Kawakami, Hisato, Sakiyama, Tsutomu, Okamoto, Kunio, Tanaka, Kaoru, Takeda, Masayuki, Kaneda, Hiroyasu, Nishina, Shin-ichi, Tsurutani, Junji, Fujiwara, Kimiko, Nomura, Morihiro, Yamazoe, Yuzuru, Chiba, Yasutaka, Nishida, Shozo, Tamura, Takao, Nakagawa, Kazuhiko
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Cancer therapies; Chemotherapy; Cisplatin; Cisplatin - adverse effects; Cisplatin - therapeutic use; Creatinine; Creatinine - blood; Dietary Supplements; DNA Mutational Analysis; Drug dosages; Drug therapy; Homeostasis; Humans; Hydration; Hypomagnesemia; Inflammation; Intravenous administration; Kidney Diseases - chemically induced; Kidney Diseases - prevention & control; Kidneys; Magnesium; Magnesium - pharmacology; Medicine; Medicine and Health Sciences; Multivariate Analysis; Neoplasms - drug therapy; Nonsteroidal anti-inflammatory drugs; Odds Ratio; Oncology; Patients; Pharmacy; Retrospective Studies; Risk analysis; Risk Factors; Risk reduction; Studies; Supplements; Terminology; Toxicity; University faculty
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101902

Nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. We retrospectively evaluated potential risk factors for cisplatin-induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. We reviewed clinical data for 401 patients who underwent chemotherapy including a high dose (≥60 mg/m2) of cisplatin in the first-line setting. Nephrotoxicity was defined as an increase in the serum creatinine concentration of at least grade 2 during the first course of cisplatin chemotherapy, as assessed on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The severity of nephrotoxicity was evaluated on the basis of the mean change in the serum creatinine level. Magnesium was administered intravenously to 67 patients (17%). Cisplatin-induced nephrotoxicity was observed in 127 patients (32%). Multivariable analysis revealed that an Eastern Cooperative Oncology Group performance status of 2 (risk ratio, 1.876; P = 0.004) and the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio, 1.357; P = 0.047) were significantly associated with an increased risk for cisplatin nephrotoxicity, whereas intravenous magnesium supplementation was associated with a significantly reduced risk for such toxicity (risk ratio, 0.175; P = 0.0004). The development of hypomagnesemia during cisplatin treatment was significantly associated with a greater increase in serum creatinine level (P = 0.0025). Magnesium supplementation therapy was also associated with a significantly reduced severity of renal toxicity (P = 0.012). A relatively poor performance status and the regular use of NSAIDs were significantly associated with cisplatin-induced nephrotoxicity, although the latter association was marginal. Our findings also suggest that the ability of magnesium supplementation to protect against the renal toxicity of cisplatin warrants further investigation in a prospective trial.