Intravenous Magnesium and Cisplatin-Associated Acute Kidney Injury

Importance Cisplatin-associated acute kidney injury (CP-AKI) is a frequent complication of cisplatin chemotherapy and is associated with considerable morbidity and mortality. Prophylactic administration of intravenous (IV) magnesium attenuates CP-AKI in animal models; however, its association with CP-AKI in humans has not been rigorously evaluated. Objective To evaluate the association of prophylactic IV magnesium administration with CP-AKI in patients with cancer undergoing cisplatin chemotherapy. Design, Settings, and Participants This multicenter study was conducted at 5 major cancer centers across the US and included adult patients with cancer who were treated with a first dose of IV cisplatin between 2006 to 2022. Data analyses were performed from February to December 2024. Exposure IV magnesium vs no IV magnesium receipt on the first day of cisplatin treatment. Main Outcomes and Measures Composite outcome of CP-AKI or death, with CP-AKI defined as a 2-fold or greater increase in serum creatinine levels from baseline or receipt of kidney replacement therapy within 14 days after first dose of IV cisplatin. Secondary outcomes were CP-AKI or death, defined using alternative definitions, as well as major adverse kidney events at 90 days. Inverse probability treatment weighting was used to estimate the association between IV magnesium receipt and CP-AKI. Models were adjusted for demographics, comorbidities, laboratory values, receipt of concurrent nephrotoxic anticancer therapies, site, year of cisplatin administration, and cisplatin dose. Results A total of 13 719 patients were included (median [IQR] age, 59 [49-67] years; 7817 male [57%]), of whom 3893 (28.4%) received IV magnesium on the first day of cisplatin chemotherapy. The median (IQR) dose of IV magnesium was 2 (1-2) g. CP-AKI or death occurred in 104 of 3893 patients (2.7%) who received IV magnesium, and in 520 of 9826 (5.3%) who did not (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97). Results were similar across a number of sensitivity analyses and secondary outcomes, including major adverse kidney events at 90 days. Conclusions and Relevance This multicenter cohort study found that patients with cancer who received prophylactic IV magnesium before initiating treatment with IV cisplatin had a lower risk of CP-AKI compared to those who did not receive magnesium. Randomized clinical trials are needed to confirm these findings.