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

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