他克莫司联合小剂量激素治疗儿童难治性肾病疗效及安全性的系统评价

Effectiveness and Safety of Tacrolimus combined with small dose of prednisone for refractory nephrotic syndrome in children:A Systematic Review

目的系统评价他克莫司(TAC)联合小剂量激素治疗儿童难治性肾病的疗效和安全性。方法计算机检索中国知网(CNKI)、维普、万方数据库、MEDLINE、Pub Med、The Cochrane Library、EMBASE、Up To Date,时限为建库至2014年9月,同时手工检索相关杂志及研究资料,查找TAC联合小剂量激素治疗儿童难治性肾病的随机对照试验(RCT),由两名评价者独立筛选文献、提取资料、评价质量并交叉核对,采用Rev Man5.2进行Meta分析。结果共纳入6个RCT,354例儿童患者,Meta分析结果显示总缓解率:TAC+激素(Pred)组优于单用TAC组[OR=13.29,95%CI(2.30,76.94),P=0.004],优于环磷酰胺(CTX)+Pred组[OR=4.98,95%CI(2.53,9.81),P<0.00001],不良反应:TAC+Pred组总不良反应发生率低于对照组[OR=0.26,95%CI(0.14,0.48),P<0.00001],严重不良反应发生率低于对照组[OR=0.39,95%CI(0.17,0.89),P=0.03],复发率低于单用TAC组[OR=0.06,95%CI(0.01,0.47),P=0.007],胃肠道不良反应的发生率与对照组无统计学意义[OR=0.32,95%CI(0.07,1.55),P=0.16]。结论 TAC联合小剂量激素可提高儿童难治性肾病的总缓解率,降低总不良反应和严重不良反应发生率,相比单用TAC可降低复发率,基于研究的局限性,仍需高质量的临床RCT进一步论证。

Objective To systematically evaluate the effectiveness and safety of Tacrolimus（TAC）combined with small dose ofprednisone for refractory nephrotic syndrome in children. Methods Databases including CNKI,Wan Fang Data,VIP,MEDLINE,Pub Med,the Cochrane Library,EMBASE,Up To Date,were searched from beginning time to September 2014,and relevant maga-zines and information were also searched manually. All randomized controlled trials（RCTs）about children＇s refractory nephrotic syn-drome were independently collected and evaluated by two reviewers,the meta-analysis was performed using Rev Man5.2. Results 6RCTs involving 354 children with refractory nephrotic syndrome were included. The results of meta-analysis showed the total remis-sion.in the TAC＋ Pred group was higher than that in TAC group [OR=13.29,95%CI（2.30,76.94）,P=0.004],and higher than that inthe CTX＋Pred group [OR=4.98,95%CI（2.53,9.81）,P〈0.00001]. The total incidence rate of adverse reaction in the TAC＋ Predgroup was lower than that in control group[OR=0.26,95%CI（0.14,0.48）,P〈0.00001]. The serious incidence rate of adverse reactionin the TAC＋ Pred group was lower than that in control group[OR=0.39,95%CI（0.17,0.89）,P=0.03],the recurrence rate in theTAC＋ Pred group was lower than that in only TAC group[OR=0.06,95%CI（0.01,0.47）,P=0.007]. There were no significant differ-ences in the incidence rate of gastrointestinal adverse reaction between the TAC＋ Pred group and control group[OR=0.32,95%CI（0.07,1.55）,P=0.16]. Conclusion Tacrolimus combined with small dose of prednisone in treating refractory nephrotic syndrome of children can increase the total remission rate and decrease the total and serious incidence rate of adverse reaction. The recurrence ratewas reduced compared with the TAC group. But a high-quality clinical RCT is still needed based on the limitation of the study