他克莫司与环磷酰胺治疗特发性膜性肾病的系统评价

Systematic Review of Tacrolimus and Cyclophosphamide in Treatment of Idiopathic Membranous Nephropathy

目的：系统评价他克莫司（FK506）与环磷酰胺（cyclophosphamide,CTX）治疗特发性膜性肾病（idiopathic membranous nephropathy,IMN）的有效性和安全性。方法：计算机检索中国期刊全文数据库、中国生物医学文献数据库、万方数据库、维普中文科技期刊、Pub Med、MEDLINE、Cochrance Library等数据库,筛选FK506与CTX治疗IMN的随机对照试验,采用Review Manager 5.3软件对纳入文献进行荟萃（Meta）分析。结果：最终纳入10篇文献,包括490例IMN患者。Meta分析结果显示：治疗6个月后,FK506组患者的完全缓解率（CR）（OR=2.28,95%CI=1.53~3.42,Z=4.02,P〈0.001）、总缓解率（RR）（OR=2.19,95%CI=1.46~3.31,Z=3.76,P=0.000 2）均明显优于CTX组,差异有统计学意义;治疗12个月后,FK506组与CTX组患者的CR（OR=1.10,95%CI=0.43~2.81,Z=0.2,P=0.85）、RR（OR=1.22,95%CI=0.41~3.67,Z=0.36,P=0.72）的差异无统计学意义。对纳入9个随机对照试验治疗安全性的评价结果显示,FK506组与CTX组患者糖耐量异常（OR=2.08,95%CI=1.10~3.94,Z=2.26,P=0.02）、骨髓抑制（OR=0.13,95%CI=0.03~0.52,Z=2.89,P=0.004）、感染（OR=0.40,95%CI=0.23~0.70,Z=3.23,P=0.001）和肝损害（OR=0.48,95%CI=0.24~0.94,Z=2.21,P=0.03）发生率的差异有统计学意义,2组患者胃肠道反应、脱发和高血压发生率的差异无统计学意义（P〉0.05）。结论：与经典治疗药物CTX相比,FK506能显著提高IMN患者的短期缓解率。FK506更易引起糖耐量异常和肝损害,在安全性方面无明显优势。

OBJECTIVE：To systematically review the efficacy and safety of tacrolimus（FK506） and cyclophosphamide（CTX） in treatment of idiopathic membranous nephropathy（IMN）.METHODS：CJFD,Chinese Biological and Medical Database,Wanfang Database,VIP Database,Pub Med,MEDLINE and Cochrance Library,etc,were retrieved to screen the ramdomized control trials（RCT） of FK506 and CTX in treatment of IMN,Metaanalysis was performed by Review Manager 5.3 software.RESULTS：There were totally 10 literatures,including490 cases of IMN.The result of Meta-analysis showed that,after treatment of 6 months,the CR and RR of FK506 were respectively（OR = 2.28,95% CI = 1.53-3.42,Z = 4.02,P 〈0.001） and（OR = 2.19,95% CI = 1.46-3.31,Z = 3.76,P = 0.000 2）,significantly higher than that of control group,with statistical significance.After treatment of12 months,there was no statistical significance between FK 506 group and CXT group with CR（OR = 1.10,95% CI =0.43-2.81,Z = 0.2,P = 0.85） and RR（OR = 1.22,95% CI = 0.41-3.67,Z = 0.36,P = 0.72）.According to the evaluation of treatment safety in 9 RCT,the differences of incidence of abnormal glucose metabolism（OR = 2.08,95%CI = 1.10-3.94,Z = 2.26,P = 0.02）,myelosuppression（OR = 0.13,95% CI = 0.03-0.52,Z = 2.89,P = 0.004）,infection（OR = 0.40,95% CI = 0.23-0.70,Z = 3.23,P = 0.001） and liver injury（OR = 0.48,95% CI = 0.24-0.94,Z = 2.21,P = 0.03） were statistically significant between FK 506 group and CXT group;yet there was no statistical significance in incidence of gastrointestinal reaction,alopecia and hypertensive between two groups（P〉 0.05）.CONCLUSIONS：Compared with the classical drug of CTX,FK 506 can significantly improve the short-term relief rate of patients with IMN.And FK 506 has a high incidence of abnormal glucose metabolism and liver injury with nosignificant advantage in safety.