Prophylactic IV magnesium before initiating treatment with IV cisplatin appears to lower the risk of cisplatin-associated acute kidney injury (CP-AKI) in adults with cancer, according to a US cohort study.

While RCTs are warranted to confirm the findings, the study suggests a simple and cost effective strategy to mitigate a frequent and serious complication of cisplatin use.

A US study, published in JAMA Oncology [link here], comprised 13,719 patients initiating cisplatin treatment between 2006 and 2022 at one of five cancer centres. More than a quarter (28%) of patients received IV magnesium, with a median dose of 2g, on the day of cisplatin initiation. 

The study found 2.7% of patients who received magnesium developed moderate-severe CP-AKI or died within 14 days. In comparison, 5.3% of those who did not receive magnesium developed the primary outcome of CP-AKI or death.

“Patients who received IV magnesium had a lower odds of CP-AKI (adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97) compared to patients who did not receive IV magnesium.”

It found the magnitude of benefit from IV magnesium was higher in younger patients <65 years versus older patients and in females versus males. 

“There was also effect modification based on eGFR (<90: OR, 0.89 [95% CI, 0.70-1.14]; ≥90: OR, 0.67 [95% CI, 0.52-0.87]; P = .05) and serum magnesium levels (1.4-1.9 mg/dL: OR, 0.99 [95% CI, 0.74-1.31]; 2.0-2.2 mg/dL: OR, 0.67 [95% CI, 0.52-0.87]; P = .04), where patients with higher eGFR and higher baseline serum magnesium levels appeared to benefit the most from IV magnesium.”

“IV magnesium-treated patients also had a lower risk of MAKE90 compared to those not treated with IV magnesium,” the study said.

The investigators, led by director of onconephrology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute Dr Shruti Gupta, said their findings were biologically plausible and consistent with preclinical findings in which magnesium deficiency increases susceptibility to CP-AKI and prophylactic administration of IV magnesium attenuates it.

“Magnesium deficiency downregulates efflux transporters expressed on the apical side of kidney proximal tubular cells (eg, multidrug resistance proteins 4 and 6), resulting in increased intracellular platinum accumulation. Administration of magnesium restores expression of these transporters, promoting the excretion of platinum in the urine.”

“The findings of this multicentre cohort study suggest that prophylactic administration of IV magnesium – a safe, inexpensive, and readily available intervention – was independently associated with a lower risk of CP-AKI in patients with cancer initiating cisplatin chemotherapy,” they concluded.