Abstract: 　Background　Diabetes mellitus is an important factor leading to cardiovascular events and end-stage renal disease.Although it has been confirmed that many drugs may reduce proteinuria in patients with diabetic nephropathy and delay the progression of nephropathy，their adverse reactions limit clinical application.As a new attempt to treat diabetic nephropathy，endothelin antagonists have been paid more and more attention.Objective　To evaluate the effectiveness and safety of endothelin receptor-antagonists in patients with diabetic nephropathy.Methods　Wanfang Data Knowledge Service Platform，CNKI，VIP，PubMed，EMBase，Cochrane Library and other databases were retrieved as of October 2018 for randomized controlled trials（RCTs）of endothelin-receptor antagonists for diabetic nephropathy，and RCTs listed as references of the RCTs in the databases in printed form，and related conference records in printed form were also reviewed.RCTs inclusion，data extraction and quality assessment were performed by using the Cochrane methods for conducting systematic reviews by two researchers independently.When differences of views arise，the decision is made by the third person evaluation.RevMan 5.3 was used for meta-analysis of aspects〔all-cause mortality，incidence rate of cardiovascular disease，urinary protein，estimated glomerular filtration rate（eGFR），incidence rates of adverse reactions and severe adverse reactions〕determining effectiveness and safety.Results　Six RCTs involving 2 082 patients were included for analysis.Meta-analysis showed that endothelin-receptor antagonists could reduce urinary protein levels in patients with diabetic nephropathy 〔SMD=-0.66，95%CI（-0.76，-0.56），P<0.000 01〕，but could not reduce all-cause mortality〔RR=1.49，95%CI（0.81，2.76），P=0.20〕.Although endothelin-receptor antagonists group and placebo group showed no significant difference in the incidence rate of adverse reactions〔RR=1.06，95%CI（0.99，1.13），P=0.08〕，endothelin-receptor antagonists group had much higher incidence rates of severe adverse reactions〔RR=1.34，95%CI（1.12，1.61），P=0.001〕and cardiovascular diseases〔RR=1.45，95%CI（1.07，1.97），P=0.02〕.Endothelin-receptor antagonists group demonstrated much lower systolic blood pressure〔MD=-3.88，95%CI（-5.36，-2.40），P=0.000 1〕，diastolic blood pressure〔MD=-2.65，95%CI（-4.30，-1.01），P=0.002〕，and hemoglobin level〔MD=-0.69，95%CI（-0.87，-0.51），P=0.000 1〕than placebo group.Conclusion　Endothelin-receptor antagonists can reduce urinary protein level in patients with diabetic nephropathy.But their long-term efficacy and safety need to be confirmed by RCTs with larger sample sizes.

Key words: Diabetic nephropathy, Endothelin-receptor antagonists, Systematic review, Meta-analysis, Adverse drug reaction, Cardiovascular diseases

摘要： 背景　糖尿病是导致心血管疾病和终末期肾病的重要因素。尽管研究证实很多药物可能降低糖尿病肾病患者尿蛋白水平，延缓肾病进展，但是其不良反应限制了其临床应用。而内皮素拮抗剂作为治疗糖尿病肾病的一种新的尝试，逐渐受到关注。目的　评估内皮素拮抗剂治疗糖尿病肾病的临床疗效和安全性。方法　检索万方数据知识服务平台、中国知网（CNKI）、维普网、PubMed、EMBase、Cochrane Library等数据库，并手工检索会议记录和纳入研究的参考文献，获得内皮素拮抗剂治疗糖尿病肾病的随机对照试验（RCT），检索起止时间为建库至2018年10月。根据Cochrane手册提供的方法，由两人独立提取数据、进行数据评估，出现分歧时由第三人评估决定。应用RevMan 5.3 软件进行Meta分析，并对全因死亡率、心血管疾病发生率、尿蛋白、估算肾小球滤过率（eGFR）、不良反应发生率、严重不良反应事件发生率等进行比较。结果　最终纳入6篇RCT，共2 082例患者。Meta分析结果显示，内皮素拮抗剂能够降低糖尿病肾病患者的尿蛋白水平〔标准均数差（SMD）=-0.66，95%CI（-0.76，-0.56），P<0.000 01〕，但是不能降低患者全因死亡率〔风险比（RR）=1.49，95%CI（0.81，2.76），P=0.20〕。尽管内皮素拮抗剂和安慰剂的不良反应事件发生率上无统计学差异〔RR=1.06，95%CI（0.99，1.13），P=0.08〕，但是内皮素拮抗剂严重不良反应事件发生率〔RR=1.34，95%CI（1.12，1.61），P=0.001〕和心血管疾病发生率〔RR=1.45，95%CI（1.07，1.97），P=0.02〕高于安慰剂。内皮素拮抗剂治疗糖尿病肾病患者收缩压〔均数差（MD）=-3.88，95%CI（-5.36，-2.40），P=0.000 1〕、舒张压〔MD=-2.65，95%CI（-4.30，-1.01），P=0.002〕、血红蛋白水平〔MD=-0.69，95%CI（-0.87，-0.51），P=0.000 1〕低于安慰剂。结论　内皮素拮抗剂能够降低糖尿病肾病患者尿蛋白，但是需要大样本RCT证实内皮素拮抗剂的长期疗效和不良反应。

关键词: 糖尿病肾病, 内皮素拮抗剂, 系统评价, Meta分析, 药物不良反应, 心血管疾病