Background: Endothelin receptor antagonists (ERAs) are considered a potential effective treatment to reduce proteinuria and protect kidney function for patients with chronic kidney disease (CKD); however, they may cause fluid retention. We conducted this meta-analysis to quantify the efficacy and safety of ERAs in CKD. Methods: We searched Cochrane Library, Ovid Medline, and Ovid Embase for randomized controlled trials up to January 2025. Continuous and dichotomous data were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs) and risk ratios (RRs) with 95% Cis, respectively. Results: Fourteen trials enrolling 6,412 patients were included. Compared to the control group, ERAs decreased the risk of end-stage kidney disease (ESKD) RR=0.76, 95%CI (0.61, 0.96), reduced the urine protein-to-creatinine ratio (UPCR) SMD=-0.56, 95%CI (-0.78, -0.35) and urine albumin-to-creatinine ratio (UACR) SMD=-0.64, 95%CI (-0.75, -0.53), achieved more frequent complete proteinuria remission RR=2.61, 95%CI (1.84, 3.71) and partial proteinuria remission RR=1.51, 95%CI (1.32, 1.73), slowed the decline of estimated glomerular filtration rate (eGFR) in the subgroup with a follow-up duration of at least one year SMD=0.18, 95%CI (0.04, 0.32), improved the chronic eGFR slope SMD=0.15, 95%CI (0.01, 0.30), and decreased systolic blood pressure SMD=-0.53, 95%CI (-0.76, -0.30) and diastolic blood pressure SMD=-0.78, 95%CI (-1.18, -0.38). Although the risk was increased in B-type natriuretic peptide (BNP) SMD=0.08, 95%CI (0.01, 0.16) and body weight SMD=0.15, 95%CI (0.01, 0.29), ERAs did not increase the incidence of edema, fluid retention, or heart failure. The risk of hypotension was higher with ERAs compared to the control group RR=1.92, 95%CI (1.36, 2.70). Conclusion: These findings suggest that ERAs may reduce proteinuria, prevent kidney disease progression, and lower blood pressure in individuals with CKD.
Yw et al. (Mon,) studied this question.