环孢素A治疗特发性膜性肾病的荟萃分析

摘要

Objective Since there is no consensus regarding a standard treatment of idiopathic membranous nephropathy(IMN), cyclosporine A(CsA) has emerged as an immunosuppressant for treating IMN. A systematic review and Meta-analysis were performed to determine the treatment efficacy and toxicity outcomes of CsA in IMN. Methods Publications in the English and Chinese literature were searched with the keywords ' cyclosporine', 'idiopathic', 'glomerulonephritis', 'membranous', 'membranous nephropathy ', 'membranous glomerulopathy', ' membranous glomerulonephropathy ', ' idiopathic membranous nephropathy ', ' idiopathic membranous glomerulonephritis' for clinical trials in electronic databases. Primary outcome was relative risk of total or complete renal remission at the end of follow-up. Secondary outcome included RRs of relapse, development of end-stage renal disease(ESRD) , deterioration of renal function and hypertension. Results Five randomized controlled trials(RCTs) and three clinical controlled trials (CCTs) involving 392 patients were included. CsA offers better efficacy in inducing complete remission than other regimens ( RR =1.60,95% CI =1.18 - 2.18, P＜0. 01). But CsA did not increase total renal remission rates as compared to other regimens ( RR = 1. 15, 95 % CI = 0. 86 - 1. 53 , P＞0. 05 ). After removing the Kosmadakis trial whose follow-up was less than 1 year, the total renal remission rate was also higher in patients receiving CsA compared with those with other regimens( RR = 1. 39, 95% CI = 1. 17 - 1. 67, P＜0. 01). There are no significant difference between patients receiving CsA and other regimens in the risks of hypertension, ESRD and relapse. However,the risks of renal function deterioration tended to be higher in the CsA group( RR =1. 53, 95% CI =1. 04 - 2. 25, P＜0. 05). Conclusion CsA has higher efficacy in inducing complete renal remission in IMN than other regimens. But CsA treatment may deteriorate the renal function which recovers after dosage reduction or discontinuation. So CsA may be considered as a first-line or an alternative for therapy of IMN.%目的 特发性膜性肾病(idiopathic membranous nephropathy,IMN)的合理治疗仍有争议,本研究应用荟萃分析(Meta分析)对环孢素A治疗IMN的多个独立研究结果进行综合分析,评价环孢素A治疗特发性膜性肾病的临床疗效和不良反应.方法 系统检索Cochrane图书馆的临床试验注册中心、PUBMED、EMBASE、中国期刊全文数据库(CNKI)和万方数据库中关于环孢素A治疗IMN的随机对照试验(randomized controlled trials,RCTs)或临床对照试验(clinical controlled trials,CCTs).以完全缓解率、总缓解率(完全缓解率和部分缓解率之和)为主要观察指标,以复发率、肾功能恶化、新增高血压或降压药加量、终末期肾病(end-stage renal disease,ESRD)的发生率为次要观察指标.使用相对危险度(relative risk,RR)进行计算评估以上观察指标.结果 合计8篇RCT或CCT,共392例患者,纳入本次分析.Meta分析结果显示,环孢素A治疗组与对照组相比,可提高IMN的完全缓解率(RR =1.60,95％ CI =1.18～2.18,P＜0.01),总缓解率差异无统计学意义(RR =1.15,95％ CI =0.86～1.53,P＞0.05).剔除随访时间小于1年的Kosmadakis等研究,再行Meta分析,与对照组相比,环孢素A可提高IMN的总缓解率(RR=1.39,95％ CI =1.17～1.67,P＜0.01).环孢素A较其他治疗组,在复发率、新增高血压和降压药加量、终末期肾病的发病率方面差异无统计学意义,但是可引起肾功能一过性恶化(RR =1.53,95％-CI =1.04～2.25,P＜0.05),停药或药物减量后缓解.结论 目前证据表明,环孢素A可作为治疗IMN的一线或替代药物.