Dose matters: a dose-stratified real-world analysis of magnesium sulfate in preventing cisplatin-induced nephrotoxicity

BACKGROUND: Intravenous magnesium supplementation is increasingly adopted as a nephroprotective measure in patients receiving cisplatin-based chemotherapy, particularly in several Asian and European oncology centers. However, the dose-dependent nature of this effect remains poorly defined, and most studies have not addressed long-term renal outcomes. METHODS: In this multicenter retrospective study, 287 patients undergoing weekly cisplatin-based chemoradiotherapy for head and neck or cervical cancer were stratified based on prophylactic magnesium dose: 12 mEq or 24 mEq IV magnesium sulfate. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) were measured at baseline, during treatment, and up to 12 months post-treatment. The incidence of acute kidney injury (AKI) was defined using CTCAE v5.0 criteria. Comparative analysis was performed using standard statistical tests, and results were contextualized with recent large-scale cohort findings. RESULTS: AKI incidence was 17.7% in the 12 mEq group and 13.2% in the 24 mEq group (p = 0.32). However, longitudinal renal follow-up revealed a significant divergence in sCr and eGFR trajectories: the 24 mEq cohort maintained near-baseline renal function, whereas the 12 mEq group exhibited progressive deterioration at 6 and 12 months. These findings contrast with prior binary exposure studies and indicate a sustained, dose-dependent protective effect. CONCLUSIONS: Magnesium's renoprotective benefit in cisplatin-based therapy is not only determined by its presence, but also by its dose. Our results support the incorporation of standardized magnesium dosing, specifically a minimum of 24 mEq, into clinical protocols. Dose precision, not merely inclusion, should guide prophylactic strategies to ensure effective renal protection.