Meta-Analysis of Randomized Controlled Trials Assessing the Efficacy and Safety of Endothelin Receptor Antagonists in CKD
A meta-analysis of 14 trials (6,412 patients) found endothelin receptor antagonists reduced the risk of kidney failure and proteinuria in chronic kidney disease, though they raised the risk of low blood pressure.
Background
Endothelin-1 drives vasoconstriction, inflammation, and fibrosis in the kidney. Endothelin receptor antagonists (ERAs) reduce proteinuria but can cause fluid retention, raising heart-failure concerns. This meta-analysis quantified their efficacy and safety in chronic kidney disease using randomized trials identified through January 2025.
Key findings
Fourteen trials enrolling 6,412 patients showed ERAs reduced the risk of ESKD (RR 0.76, 95% CI 0.61-0.96), lowered urine protein-to-creatinine (SMD -0.56) and albumin-to-creatinine ratios (SMD -0.64), achieved more frequent complete (RR 2.61) and partial (RR 1.51) proteinuria remission, slowed eGFR decline in trials followed at least 1 year, and reduced systolic and diastolic blood pressure.
Safety
ERAs did not increase edema, fluid retention, or heart failure overall, but the risk of hypotension was nearly doubled (RR 1.92, 95% CI 1.36-2.70), with small increases in B-type natriuretic peptide and body weight.
Clinical implications
The authors recommend ETA receptor-selective ERAs for patients with CKD whose proteinuria and risk of progression remain insufficiently controlled, with consideration of combination therapy with SGLT2 inhibitors to mitigate fluid-related adverse effects.
Category
Research
Source
Clinical Journal of the American Society of Nephrology (CJASN)
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