# The Emerging Role of Magnesium in Preventing Acute Kidney Disease During Concurrent Chemoradiotherapy in Head and Neck Cancer

## TL;DR

This study shows that magnesium supplementation may help protect kidney function in head and neck cancer patients undergoing cisplatin-based treatment.

## Contribution

The study provides real-world evidence that intravenous magnesium may reduce cisplatin-induced kidney injury in head and neck cancer patients.

## Key findings

- Acute kidney disease occurred in 5.3% of patients receiving high-dose cisplatin with magnesium.
- Lower baseline kidney function, higher BMI, and RAAS inhibitor use were linked to increased AKD risk.
- Magnesium supplementation was well tolerated and associated with reduced kidney injury.

## Abstract

Cisplatin is widely used in the treatment of head and neck cancer, but its use is often limited by kidney toxicity. Acute kidney disease is a condition that can appear after cisplatin exposure and may compromise treatment completion and long-term outcomes. In this study, we prospectively followed patients receiving high-dose cisplatin with radiotherapy under a standardized supportive care protocol that included intravenous magnesium. We observed that some patients still developed kidney problems, and that lower baseline kidney function, higher body weight, and the exposure to selected medications were linked to a greater risk. Magnesium supplementation was well tolerated and was associated with reduced kidney injury. These results underline the importance of careful monitoring and provide evidence that magnesium could be a simple and accessible strategy to improve the renal safety of cisplatin-based therapy in head and neck cancer.

Background: High-dose cisplatin (≥200 mg/m2 cumulative) remains the standard of care in concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its use is frequently limited by nephrotoxicity, including acute kidney disease (AKD). This recently described clinical renal syndrome encompasses functional alterations of the kidney lasting fewer than 3 months post-exposure. Although hydration protocols and antiemetic strategies are routinely applied to avoid reduction in oral liquid intake and to prevent dehydration that could worsen renal function, AKD continues to pose a threat to reach the therapeutic dose, to treatment completion, and long-term outcomes. Recent evidence supports the nephroprotective role of intravenous (IV) magnesium in mitigating cisplatin-induced tubular injury, yet prospective data on its impact in real-world LA-HNSCC settings remain limited. We aimed to prospectively investigate the incidence and characteristics of renal impairment, particularly AKD, in a real-world cohort of LA-HNSCC patients treated with high-dose cisplatin and standardized supportive therapy, including intravenous magnesium. Methods: We conducted a prospective observational study including 207 patients with LA- HNSCC undergoing high-dose cisplatin-based CRT (≥200 mg/m2 cumulative dose), within a standardized supportive care protocol incorporating IV magnesium. Renal function was assessed over three cycles via serum creatinine and estimated glomerular filtration rate (eGFR). AKD was defined and staged according to KDIGO criteria. Clinical and biochemical predictors of AKD were explored. Results: AKD occurred in 5.3% of patients (11/207; 95% CI 2.7–9.3), with eight events between C1→C2, 3 between C2→C3, and 0 thereafter; recovery at the next cycle was 9.1% (1/11). Among them, 57.1% were classified as stage 1. A baseline eGFR < 90 mL/min/1.73 m2 was associated with a higher AKD incidence (13.3% vs. 5.4%). Body mass index (BMI) was significantly associated with AKD in univariate analysis (p = 0.02), whereas no independent predictor emerged in multivariate analysis. Use of renin–angiotensin–aldosterone system (RAAS) inhibitors was more frequent among patients who developed AKD (p = 0.04). Renal function declined more steeply in AKD patients, with a median eGFR slope of −0.3917 mL/min/1.73 m2/day vs. −0.0483 mL/min/1.73 m2/day in those without AKD (p = 0.0005), irrespective of CKD stage. Conclusions: In a real-world cohort receiving high-dose cisplatin with structured nephroprotection including IV magnesium, AKD developed in approximately 10% of patients. Lower baseline eGFR, elevated BMI, and RAAS inhibitor use emerged as potential risk factors. These findings reinforce the importance of proactive renal monitoring and suggest a role for magnesium supplementation as an accessible strategy to enhance renal safety in curative-intent CRT.