Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China.
Diabet Med. 2021 Jan;38(1):e14411. doi: 10.1111/dme.14411. Epub 2020 Oct 9.
To analyse the efficacy and safety of endothelin receptor antagonists for people with diabetic kidney disease.
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-effect model to calculate the mean difference or risk ratio with the 95% CI.
Seven studies with a total of 4730 participants were included. Overall, endothelin receptor antagonists significantly reduced albuminuria compared with placebo (standardized mean difference -0.48, 95% CI -0.64 to -0.33). Atrasentan, in particular, effectively reduced albuminuria (standardized mean difference -0.58, 95% CI -1.00 to -0.17) 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 -0.47, 95% CI -0.57 to -0.36) 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-response analysis indicated that 0.75 mg/day atrasentan is expected to be optimal for renoprotection, with maximal albuminuria reduction and minimal fluid retention events.
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 mg/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).
分析内皮素受体拮抗剂在糖尿病肾病患者中的疗效和安全性。
通过 PubMed、Embase 和 Cochrane 图书馆，检索比较内皮素受体拮抗剂与安慰剂在糖尿病肾病患者中的随机对照试验。采用随机效应模型计算均数差或风险比及其 95%CI。
共纳入 7 项研究，总计 4730 名参与者。总体而言，与安慰剂相比，内皮素受体拮抗剂可显著减少蛋白尿（标准化均数差-0.48，95%CI-0.64 至-0.33）。阿曲生坦尤其能有效降低蛋白尿（标准化均数差-0.58，95%CI-1.00 至-0.17）和复合肾脏终点事件的风险（风险比 0.65；95%CI 0.49 至 0.88），充血性心力衰竭（风险比 1.40，95%CI 0.76 至 2.56）和死亡率（风险比 1.11，95%CI 0.77 至 1.61）的发生率无显著变化。相比之下，尽管阿伏生坦能降低蛋白尿（标准化均数差-0.47，95%CI-0.57 至-0.36）和复合肾脏终点事件的风险（风险比 0.63，95%CI 0.42 至 0.94），但与充血性心力衰竭风险的显著增加（风险比 2.61，95%CI 1.36 至 5.00）和死亡率风险的无显著增加（风险比 1.50，95%CI 0.81，2.78）相关。波生坦的疗效或安全性结果没有显著变化。剂量-反应分析表明，每天 0.75 毫克阿曲生坦可能是最佳的肾脏保护剂量，具有最大的蛋白尿减少和最小的液体潴留事件。在未来的临床实践中，需要警惕充血性心力衰竭风险。（PROSPERO 注册号：CRD42020169840）。
