新型免疫抑制剂治疗特发性膜性肾病的Meta分析

Meta-analysis of novel immunosuppressants in treatment of idiopathic membranous nephropathy

目的评价新型免疫抑制剂治疗表现为肾病综合征的成人特发性膜性肾病(IMN)的有效性和安全性。方法检索Cochrane图书馆、PubMed、Embase从建馆(库)至2013年12月收录的期刊文献及资料。纳入随机对照试验(RCT)的试验组为新型免疫抑制剂,对照组为糖皮质激素联合烷化剂(苯丁酸氮芥或环磷酰胺)。采用Cochrane偏倚风险方法评价研究质量。使用倒方差法随机效应模型评估全因死亡率或进展至终末期肾脏病(ESRD)风险、肾功能下降率、完全或部分缓解率、蛋白尿以及导致停药或住院的不良事件发生率等指标。数据合并采用RevMan 5.2软件。有效性及安全性用风险比(RR)及其95%可信区间(95%CI)表示,文献发表偏倚用漏斗图分析。结果共入选9项RCT(383例患者),涉及环孢素、他克莫司、吗替麦考酚酯、促肾上腺皮质激素(ACTH)等新型免疫抑制剂。与经典的糖皮质激素联合烷化剂相比,新型免疫抑制剂不能降低全因死亡率或进展至ESRD风险[3项RCT,104例患者,RR=1.37(0.52,3.61),P=0.53];不能降低肾功能下降率[3项RCT,104例患者,RR=1.19(0.78,1.81),P=0.42];不能提高完全或部分缓解率[8项RCT,349例患者,RR=1.01(0.79,1.30),P=0.93];不能降低蛋白尿[5项RCT,175例患者,MD=-0.45(-1.56,0.66)g/d,P=0.43]。新型免疫抑制剂组与经典的糖皮质激素联合烷化剂组比较导致停药或住院的不良事件发生率的差异无统计学意义[5项RCT,80例患者,RR=0.80(0.49,1.32),P=0.39]。但亚组分析表明新型免疫制剂可显著增加完全或部分缓解率[6项RCT,240例患者,RR=1.21(1.03,1.42),P=0.02],并能显著降低蛋白尿[3项RCT,147例患者,MD=-1.35(-1.94,-0.76)g/d,P<0.0001]。结论本项Meta分析未表明新型免疫抑制剂对表现为肾病综合征的成人IMN的疗效明显优于糖皮质激素联合烷化剂。尚需开展更多的RCT进一步验证亚组分析的结果。

Objective Toassesstheefficacyandsafetyofnovelimmunosuppressantsinthe treatmentofadultidiopathicmembranousnephropathy（IMN）withnephroticsyndrome.Methods The Cochrane library,PubMed,and Embase were searched（ December 2013）to identify randomized controlled trials （ RCTs ） that compared novel immunosuppressants with corticosteroid plus alkylating agents （ chlorambucil or cyclophosphamide ）. The Cochrane-recommended bias risk tool was used to assess the quality of studies. The inverse-variance random-effects method was used to assess all-cause mortality or the risk of progression to end-stage renal disease（ ESRD）,the rate of decline in renal function,complete or partial remission,proteinuria,and adverse events leading to discontinuation or hospitalization. Data were synthesized with the RevMan software version 5. 2. The effect of treatment was presented with risk ratio （rr）and 95﹪ confidence interval（95﹪ CI）,and the publication bias was analyzed with funnel plot. Results NineRCTswith383patientswereincluded.The novel immunosuppressants included were cyclosporine,tacrolimus,mycophenolate mofetil,and adrenocorticotropic hormone（ ACTH）. Compared to classical therapy of corticosteroid plus alkylating agents,novel immunosuppressants did not significantly reduce the all-cause mortality or the risk of progression to ESRD[3 RCTs,104 patients,rr=1. 37（0. 52,3. 61）,P=0. 53],did not decrease the rate of decline in renal function[3 RCTs,104 patients,rr=1. 19（0. 78,1. 81）, P=0. 42],did not improve complete or partial remission[8 RCTs,349 patients,rr=1. 01（0. 79,1. 30）,P=0. 93],or did not reduce proteinuria[5 RCTs,175 patients,MD= -0. 45（-1. 56,0. 66）g/day,P=0. 43]. There was no difference between the two groups in the risk of adverse events leading to discontinuation or hospitalization[5 RCTs,80 patients,rr =0. 80（0. 49,1. 32）,P =0. 39]. However,subgroup analyses indicated that the novel immunosuppressants significantly increased complete or partial remission[ 6 RCTs, 240 patients,rr=1. 21（1. 03,1. 42）,P=0. 02]and decreased proteinuria[3 RCTs,147 patients,MD=-1.35（-1.94,-0.76）g/day,P〈0.00001].Conclusions Thismeta-analysisdidnotindicatethatthe efficacy of novel immunosuppressants was superior to that of corticosteroid plus alkylating agents in treating adult IMN with nephrotic syndrome. More RCTs are needed to confirm the results from subgroup analyses.