Rossi R, Ehrich J H
University Children's Hospital Münster, Germany.
Eur J Clin Pharmacol. 1993;44 Suppl 1:S43-5. doi: 10.1007/BF01428392.
Ten out of 79 patients treated with ifosfamide (IFO) developed a complete (n = 2) or partial (n = 8) de Toni-Debré-Fanconi syndrome (RFS). All but one of these patients had been treated in addition with cisplatinum (CPL) or had undergone radiotherapy to the abdomen or nephrectomy as part of the overall treatment for malignancy. A detailed nephrological work-up of proximal tubular function showed decreased fractional phosphate and percent aminoacid reabsorption in 37.1 and 56.7% of cases, respectively, and the excretion of alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase was elevated in 44.4 and 23.5%. Glomerular function was well preserved in the majority of patients. Tubular dysfunction was confirmed by silver-stained SDS PAGE of urine which showed mostly low molecular weight proteinuria. CPL has been shown to result in renal magnesium loss and reduced glomerular filtration rate, and its toxicity clearly differs from IFO-mediated tubulopathy. Our data suggest that subclinical impairment of proximal tubular function was significantly increased by additional CPL therapy. We conclude that CPL may enhance IFO-mediated nephrotoxicity and that a substantial number of patients is at risk of developing persistent tubular dysfunction leading to metabolic bone disease.
79例接受异环磷酰胺（IFO）治疗的患者中有10例出现了完全性（n = 2）或部分性（n = 8）的德托尼 - 德布雷 - 范科尼综合征（RFS）。除1例患者外，其余所有患者还接受了顺铂（CPL）治疗，或作为恶性肿瘤整体治疗的一部分接受了腹部放疗或肾切除术。对近端肾小管功能进行的详细肾脏病学检查显示，分别有37.1%和56.7%的病例中，磷酸盐分数重吸收和氨基酸重吸收百分比降低，α1 - 微球蛋白和N - 乙酰 - β - D - 氨基葡萄糖苷酶的排泄分别在44.4%和23.5%的病例中升高。大多数患者的肾小球功能保持良好。通过尿液银染SDS - PAGE证实了肾小管功能障碍，其显示大多为低分子量蛋白尿。已表明CPL会导致肾脏镁流失和肾小球滤过率降低，其毒性明显不同于IFO介导的肾小管病。我们的数据表明，额外的CPL治疗显著增加了近端肾小管功能的亚临床损害。我们得出结论，CPL可能会增强IFO介导的肾毒性，并且大量患者有发生持续性肾小管功能障碍并导致代谢性骨病的风险。
