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Med."],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To analyse the efficacy and safety of endothelin receptor antagonists for people with diabetic kidney disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Randomized controlled trials comparing endothelin receptor antagonists with placebo in people with diabetic kidney disease were identified through PubMed, Embase and the Cochrane Library. We used a random\u2010effect model to calculate the mean difference or risk ratio with the 95% CI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven studies with a total of 4730 participants were included. Overall, endothelin receptor antagonists significantly reduced albuminuria compared with placebo (standardized mean difference \u20130.48, 95% CI \u20130.64 to \u20130.33). Atrasentan, in particular, effectively reduced albuminuria (standardized mean difference \u20130.58, 95% CI \u20131.00 to \u20130.17) and the risk of composite renal endpoints (risk ratio 0.65; 95% CI 0.49 to 0.88), with insignificant change in the rate of congestive heart failure (risk ratio 1.40, 95% CI 0.76 to 2.56) and mortality (risk ratio 1.11, 95% CI 0.77 to 1.61). In contrast, although avosentan reduced albuminuria (standardized mean difference \u20130.47, 95% CI \u20130.57 to \u20130.36) and the risk of composite renal endpoints (risk ratio 0.63, 95% CI 0.42 to 0.94), it was associated with a significant increase in congestive heart failure risk (risk ratio 2.61, 95% CI 1.36 to 5.00) and an insignificant increase in mortality risk (risk ratio 1.50, 95% CI 0.81, 2.78). No significant change in efficacy or safety outcomes with bosentan was detected. Dose\u2013response analysis indicated that 0.75\u00a0mg\/day atrasentan is expected to be optimal for renoprotection, with maximal albuminuria reduction and minimal fluid retention events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among the endothelin receptor antagonists, atrasentan and avosentan, but not bosentan, are effective for renoprotection in people with diabetic kidney disease. Compared with other types and doses, atrasentan 0.75\u00a0mg\/day is the most promising, with maximal albuminuria reduction and minimal fluid retention. Vigilant monitoring of congestive heart failure risk is needed in future clinical practice. (PROSPERO registration no. CRD42020169840).<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14411","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T01:16:17Z","timestamp":1601514977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Efficacy and safety of endothelin receptor antagonists in type 2 diabetic kidney disease: A systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"38","author":[{"given":"Y.","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Medical College Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Medical College Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Medical College Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Medical College Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Medical College Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-420X","authenticated-orcid":false,"given":"Y. 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