Rossi R, Gödde A, Kleinebrand A, Riepenhausen M, Boos J, Ritter J, Jürgens H
Department of Pediatric Oncology, University Children's Hospital, Münster, Germany.
J Clin Oncol. 1994 Jan;12(1):159-65. doi: 10.1200/JCO.1994.12.1.159.
This study was performed to identify risk factors of ifosfamide-induced renal damage.
Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured.
Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function.
Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.
本研究旨在确定异环磷酰胺所致肾损害的危险因素。
对120例完成包括异环磷酰胺在内的化疗后至少3个月的患者进行肾功能评估。异环磷酰胺的累积剂量为2至95 g/m²（中位数为30 g/m²）。10例患者接受了单侧肾切除术；联合细胞毒性治疗包括51例使用顺铂和57例使用甲氨蝶呤。68例患者接受了庆大霉素治疗。采用Schwartz公式估算肾小球滤过率。通过葡萄糖和16种氨基酸的重吸收百分比、钠的分数排泄以及磷酸盐的分数重吸收来评估近端肾小管功能。此外，还测量了血清碳酸氢盐水平。
近端肾小管功能障碍——以肾性氨基酸丢失（66.3%）和磷酸盐丢失（38.3%）为主——比肾小球损害和酸中毒更为常见。7例患者被诊断为肾性范科尼综合征，另有15例患者出现广泛性肾小管病变。异环磷酰胺所致肾毒性呈剂量依赖性，累积异环磷酰胺剂量与磷酸盐分数重吸收之间存在弱的线性负相关。单侧肾切除术被证明是最重要的单一危险因素（发生肾性范科尼综合征的比值比为11.4），但顺铂也显著增强了异环磷酰胺介导的肾毒性。甲氨蝶呤、庆大霉素以及初次诊断时的患者年龄对肾功能无影响。
单侧肾切除术后的患者可能应限制使用异环磷酰胺化疗。
