Risk Factors for Cisplatin-Induced Nephrotoxicity and Potential of Magnesium Supplementation for Renal Protection

Abstract

BackgroundNephrotoxicity 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.Patients and MethodsWe 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%).ResultsCisplatin-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).ConclusionsA 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.

Influence of magnesium and parathyroid hormone on cisplatin-induced nephrotoxicity in esophageal squamous cell carcinoma

“…The efficacy of administering high-dose cisplatin has been confirmed; however, severe adverse events, including hematotoxicity, anorexia, nausea and nephrotoxicity have been also reported (3,6,7). Large amounts of hydration with saline, mannitol and furosemide are accepted as the standard of care for patients treated with regimens containing high-dose (≥60 mg/m 2 ) cisplatin (3,10,11). Previous studies have demonstrated that Mg supplementation also confers protective effects against cisplatin-induced nephrotoxicity (10,(20)(21)(22).…”

“…Large amounts of hydration with saline, mannitol and furosemide are accepted as the standard of care for patients treated with regimens containing high-dose (≥60 mg/m 2 ) cisplatin (3,10,11). Previous studies have demonstrated that Mg supplementation also confers protective effects against cisplatin-induced nephrotoxicity (10,(20)(21)(22).…”

“…1 and Table II). The protective effects of oral or intravenous Mg supplementation against cisplatin-induced nephrotoxicity have been reported in various types of malignancy, including in lung (10-12), head and neck (10,23,24), digestive (8,10), testicular (25), ovarian (9,24) and bladder (24) cancer. However, just a limited number of clinical reports have demonstrated the protective effects of intravenous Mg supplementation against cisplatin-induced nephrotoxicity in ESCC (10).…”

“…Kidera et al (10) suggested that Mg supplementation was effective for protecting against renal toxicity induced by cisplatin. They also demonstrated that nephrotoxicity was more likely for patients with esophageal cancer.…”

“…This Mg depletion has been demonstrated to further enhance renal platinum accumulation and cisplatin-induced nephrotoxicity. Therefore, oral or intravenous Mg supplementation can confer renal protective effects against cisplatin-induced nephrotoxicity (8)(9)(10)(11)(12).…”