title: Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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%).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacotherapy, Kinki University Faculty of Pharmacy, Higashi-Osaka, Osaka, Japan; Department of Pharmacy, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kidera
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakiyama
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishina
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.affiliation: Department of Pharmacy, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Pharmacy, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Pharmacy, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Yamazoe
authors.affiliation: Division of Biostatistics, Clinical Research Center, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Division of Pharmacotherapy, Kinki University Faculty of Pharmacy, Higashi-Osaka, Osaka, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004252:DNA Mutational Analysis; D019587:Dietary Supplements; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008274:Magnesium / Q000494:pharmacology*; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy*; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D003404:Creatinine; D008274:Magnesium; D002945:Cisplatin