Adhikari M, Coovadia H M
Department of Paediatrics and Child Health, University of Natal, Durban.
S Afr Med J. 1994 Nov;84(11):753-6.
Cyclosporin A (CyA) has recently been shown to be effective in frequently relapsing, steroid-resistant or steroid-dependent childhood nephrotic syndrome (NS). Wider acceptance has been hindered by considerations of cost, toxicity and drug-dependent maintenance of remission. Black children in Africa with NS are mainly steroid-unresponsive and alternative therapies therefore need to be assessed. We report on 8 of 11 children who completed at least 24 weeks of CyA therapy; 6 (2 with membranous nephropathy (MEM) and 4 with focal glomerulosclerosis) showed no improvement, while 2, both with MEM, achieved remission while on CyA therapy and remained in remission for 1 and 3.5 years, respectively, after cessation of therapy. This may have been the natural course of the disease. Of the children who were unresponsive to CyA, 3 died in renal failure 8-30 months after cessation of CyA therapy, 1 had a rising creatinine value when last seen, and 2 were lost to follow-up. CyA trough levels varied between 180 and 875 ng/ml and peak levels between 563 and 1,950 ng/ml. Of 5 repeat renal biopsies, 3 were performed at the end of 24 weeks of treatment and revealed no evidence of CyA toxicity. Two biopsies revealed chronic CyA toxicity. CyA should therefore be used with caution at lower dosages and monitored at currently accepted lower trough levels in children with NS in Africa.
环孢素A（CyA）最近已被证明对频繁复发、类固醇抵抗或类固醇依赖的儿童肾病综合征（NS）有效。然而，由于成本、毒性以及缓解期对药物的依赖等因素，其广泛应用受到了阻碍。非洲患有NS的黑人儿童主要对类固醇无反应，因此需要评估替代疗法。我们报告了11名完成至少24周CyA治疗的儿童中的8名；6名（2名患有膜性肾病（MEM）和4名患有局灶性节段性肾小球硬化）无改善，而2名均患有MEM的儿童在接受CyA治疗时实现缓解，分别在治疗停止后1年和3.5年保持缓解状态。这可能是疾病的自然病程。对CyA无反应的儿童中，3名在停止CyA治疗后8 - 30个月死于肾衰竭，1名最后一次就诊时肌酐值升高，2名失访。CyA谷浓度在180至875 ng/ml之间，峰浓度在563至1950 ng/ml之间。在5次重复肾活检中，3次在治疗24周结束时进行，未发现CyA毒性证据。2次活检显示有慢性CyA毒性。因此，在非洲患有NS的儿童中，应谨慎使用较低剂量的CyA，并按照目前公认的较低谷浓度进行监测。
