Prophylactic IV Magnesium Linked to Lower Cisplatin-Associated AKI Risk

New research is shedding light on the utility of prophylactic administration of IV magnesium for reducing the risk of cisplatin-associated acute kidney injury (AKI) in patients with cancer initiating cisplatin chemotherapy.1

The multicenter study involved > 13,000 patients treated with a first dose of IV cisplatin at 5 major cancer centers across the US and found receipt of prophylactic IV magnesium was independently associated with a lower risk of cisplatin associated-AKI compared to those who did not receive magnesium.1

“Despite its clinical importance, no therapies have been shown to reliably reduce the incidence of cisplatin associated-AKI. Data from adequately powered randomized clinical trials are lacking, and observational studies have had important limitations,” Shruti Gupta, MD, MPH, an associate physician in the division of renal medicine, director of onconephrology at Brigham and Women’s Hospital/Dana-Farber Cancer Institute, and an assistant professor at Harvard Medical School, and colleagues wrote.1 “Rigorously performed studies on cisplatin associated-AKI prevention conducted with an appreciation for its underlying pathophysiologic mechanisms are therefore urgently needed.”

While cisplatin has long been the cornerstone of treatment for multiple solid cancers and remains first-line therapy for many malignant neoplasms, associated AKI often presents a serious complication. Data from preclinical studies allude to the potential of IV magnesium for attenuating cisplatin-associated AKI, but this has yet to be fully confirmed in humans.2,3

To evaluate the association of prophylactic IV magnesium administration with cisplatin associated-AKI in patients with cancer undergoing cisplatin chemotherapy, investigators examined data from a large multicenter cohort study of adults treated with a first dose of IV cisplatin between 2006 and 2022 at 5 major geographically diverse cancer centers across the US.1

The initial cohort comprised 31,082 adult patients. After exclusion of those with end-stage kidney disease, missing data on baseline serum creatinine (SCr) or magnesium levels, baseline serum magnesium levels < 1.4 or > 2.2 mg/dL, AKI at the time of cisplatin initiation compared to baseline value, and absence of ≥ 1 follow-up SCr value in the first 14 days after cisplatin initiation, the present study included 13,719 patients.1

​​The primary outcome was moderate to severe cisplatin associated-AKI or death. Cisplatin associated-AKI was defined as a ≥ 2-fold increase in SCr or receipt of kidney replacement therapy within 14 days after cisplatin receipt.1

Among the cohort, the median age was 59 (interquartile range [IQR], 49-67) years and the majority of patients were male (57%) and White (76.6%). A total of 3893 (28.4%) patients received IV magnesium on the day of cisplatin initiation. The median dose of IV magnesium was 2 (IQR, 1-2) g.1

Among patients who did not receive IV magnesium, the composite outcome occurred in 520 (5.3%) patients, of whom 460 (88.5%) developed cisplatin associated-AKI without death, 43 (8.3%) died without cisplatin associated-AKI, and 17 (3.3%) had both cisplatin associated-AKI and died within 14 days.1

Among patients who received IV magnesium, 104 (2.7%) developed the composite outcome, of whom 86 (82.7%) developed cisplatin associated-AKI without death, 10 (9.6%) died without cisplatin associated-AKI, and 8 (7.7%) had both cisplatin associated-AKI and died within 14 days.1

Upon analysis, patients who received IV magnesium had lower odds of cisplatin associated-AKI (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97) compared to patients who did not receive IV magnesium. Investigators noted results were similar across a number of sensitivity analyses and secondary outcomes, including major adverse kidney events at 90 days.1

“The findings of this multicenter 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. Randomized clinical trials are warranted to confirm these findings,” investigators concluded.1

References

1. Gupta S, Glezerman IG, Hirsch JS, et al. Intravenous Magnesium and Cisplatin-Associated Acute Kidney Injury. JAMA Oncol. doi:10.1001/jamaoncol.2025.0756

2. Solanki MH, Chatterjee PK, Gupta M, et al. Magnesium protects against cisplatin-induced acute kidney injury by regulating platinum accumulation. Am J Physiol Renal Physiol. https://doi.org/10.1152/ajprenal.00127.2014

3. Solanki MH, Chatterjee PK, Xue X, et al. Magnesium protects against cisplatin-induced acute kidney injury without compromising cisplatin-mediated killing of an ovarian tumor xenograft in mice. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00096.2015