Stöhr W, Paulides M, Bielack S, Jürgens H, Koscielniak E, Rossi R, Langer T, Beck J D
Department of Pediatric Oncology and Immunology, LESS Center, University Hospital for Children and Adolescents, Erlangen, Germany.
Pediatr Blood Cancer. 2007 Feb;48(2):140-7. doi: 10.1002/pbc.20812.
Cisplatin and carboplatin are both nephrotoxic and can induce, to a different degree, impairment in glomerular function and hypomagnesemia. Prospective longitudinal studies on these renal impairments are rare in children and adolescents.
Six hundred and fifty one sarcoma patients were investigated prospectively for nephrotoxicity in the Late Effects Surveillance System (LESS) network (median follow-up 2 years). Median cumulative dose was 360 mg/m(2) for cisplatin, and 1,500 mg/m(2) for carboplatin. Patients not treated with any platinum derivative were used as controls. Most patients (including controls) also received ifosfamide. Renal function was tested by serum magnesium, serum creatinine, and the GFR as estimated by the Schwartz formula. We evaluated incidence, dependencies, and the course of impairments.
There was no observed platinum-induced reduction of glomerular function over time. After cessation of antineoplastic therapy, hypomagnesemia (<0.7 mmol/L) occurred in 12.1% (95% CI: 6.8%-19.4%) of patients after cisplatin therapy, and in 15.6% (95% CI: 5.3%-32.8%) after carboplatin therapy, in comparison with 4.5% (95% CI: 2.0%-8.7%) in patients without any treatment with platinum derivatives (P = 0.008). In all groups, the frequency of hypomagnesemia decreased with ongoing follow-up, but serum magnesium remained lower in platinum treated patients throughout the study period.
Nephrotoxicity after treatment with cisplatin and carboplatin was mild in our study. Further studies have to show if serum magnesium is permanently decreased in platinum treated patients and if this will result in any clinically relevant impairment.
顺铂和卡铂均具有肾毒性，可不同程度地导致肾小球功能损害和低镁血症。关于儿童和青少年这些肾损害的前瞻性纵向研究较少。
在晚期效应监测系统（LESS）网络中对651例肉瘤患者进行了前瞻性肾毒性调查（中位随访2年）。顺铂的中位累积剂量为360mg/m²，卡铂为1500mg/m²。未接受任何铂类衍生物治疗的患者作为对照。大多数患者（包括对照）也接受了异环磷酰胺治疗。通过血清镁、血清肌酐以及用施瓦茨公式估算的肾小球滤过率来检测肾功能。我们评估了损害的发生率、相关性及病程。
未观察到铂类药物随时间推移导致肾小球功能降低。抗肿瘤治疗停止后，顺铂治疗后的患者中有12.1%（95%置信区间：6.8% - 19.4%）发生低镁血症（<0.7mmol/L），卡铂治疗后的患者中有15.6%（95%置信区间：5.3% - 32.8%）发生低镁血症，而未接受任何铂类衍生物治疗的患者中这一比例为4.5%（95%置信区间：2.0% - 8.7%）（P = 0.008）。在所有组中，低镁血症的发生率随随访时间的延长而降低，但在整个研究期间，铂类药物治疗的患者血清镁水平仍较低。
在我们的研究中，顺铂和卡铂治疗后的肾毒性较轻。还需进一步研究以确定铂类药物治疗的患者血清镁是否会持续降低，以及这是否会导致任何临床相关损害。
