Background: High-dose cisplatin (≥200 mg/m2cumulative) 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/m2cumulative 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 m2was 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.
背景：高剂量顺铂（累积剂量≥200 mg/m²）仍是局部晚期头颈部鳞状细胞癌（LA-HNSCC）同步放化疗（CRT）的标准治疗方案。然而，其应用常因肾毒性（包括急性肾损伤）而受限。急性肾损伤是近期被明确描述的临床肾脏综合征，指暴露于肾毒性物质后持续时间少于3个月的肾功能改变。尽管临床常规采用水化方案及止吐策略以避免口服液体摄入减少并预防可能加重肾功能损伤的脱水，但急性肾损伤仍对达到治疗剂量、完成治疗及长期预后构成威胁。近期证据表明静脉补镁具有肾保护作用，可减轻顺铂诱导的肾小管损伤，但其在真实世界LA-HNSCC治疗中影响的前瞻性数据仍有限。本研究旨在前瞻性探讨接受高剂量顺铂及标准化支持治疗（包括静脉补镁）的真实世界LA-HNSCC患者队列中肾功能损伤（尤其是急性肾损伤）的发生率与特征。 方法：我们在包含静脉补镁的标准化支持治疗框架下，开展了一项前瞻性观察性研究，纳入207例接受高剂量顺铂为基础CRT（累积剂量≥200 mg/m²）的LA-HNSCC患者。通过血清肌酐和估算肾小球滤过率（eGFR）评估三个治疗周期内的肾功能。急性肾损伤根据KDIGO标准进行定义与分期。同时探究急性肾损伤的临床与生化预测因素。 结果：5.3%的患者（11/207；95% CI 2.7–9.3）发生急性肾损伤，其中8例发生于第1至第2周期之间，3例发生于第2至第3周期之间，后续周期无新增病例；至下一周期肾功能恢复率为9.1%（1/11）。发生急性肾损伤的患者中，57.1%为1期。基线eGFR < 90 mL/min/1.73 m²与较高的急性肾损伤发生率相关（13.3% vs. 5.4%）。单因素分析显示体重指数（BMI）与急性肾损伤显著相关（p=0.02），而多因素分析未发现独立预测因素。发生急性肾损伤的患者中使用肾素-血管紧张素-醛固酮系统（RAAS）抑制剂的比例更高（p=0.04）。无论慢性肾脏病分期如何，急性肾损伤患者的肾功能下降更为显著，eGFR斜率中位数为−0.3917 mL/min/1.73 m²/天，而无急性肾损伤患者为−0.0483 mL/min/1.73 m²/天（p=0.0005）。 结论：在真实世界接受高剂量顺铂治疗并采用包含静脉补镁的结构化肾保护策略的队列中，约10%患者发生急性肾损伤。较低的基线eGFR、较高的BMI及RAAS抑制剂使用可能是潜在风险因素。这些发现强调了主动肾功能监测的重要性，并提示补镁可作为提高根治性放化疗肾脏安全性的可行策略。
肿瘤(癌症)患者之家