A recent research study, conducted by Shi and colleagues and published in the Clinical Journal of the American Society of Nephrology (ASN), highlighted compelling evidence that endothelin receptor antagonists (ERAs) offer substantial therapeutic benefits for patients with chronic kidney disease (CKD) while clarifying their safety profile—particularly regarding fluid retention concerns. GlobalData believes that this analysis validates ERAs as disease-modifying agents in CKD, offering clinically relevant benefits that extend beyond symptomatic proteinuria reduction to meaningful hard endpoints such as end-stage kidney disease (ESKD) prevention. The successful integration of ERAs into clinical practice will depend on overcoming implementation inertia through primary care engagement and demonstration of additive benefit when layered onto established four-pillar therapy in ongoing combination trials.
Conducted by researchers at Beijing Anzhen Hospital, it represents the most comprehensive synthesis to date on ERA efficacy and safety in CKD populations. The study synthesises data from 14 randomised controlled trials covering 6,412 patients, establishing ERAs as a promising intervention for reducing proteinuria, preserving kidney function, and lowering blood pressure in CKD populations. ERAs exhibited substantial nephroprotective effects, reducing ESKD risk by 24% (risk ratio [RR]=0.76, 95% confidence interval [CI] 0.61–0.96). The antiproteinuric effects proved particularly promising, with marked reductions in both urine protein-to-creatinine ratio and urine albumin-to-creatinine ratio. These findings position ERAs as promising agents for addressing proteinuria, a critical pathophysiologic driver of CKD progression. Long-term follow-up data revealed preserved glomerular filtration, with improved estimated glomerular filtration rate slopes (standardised mean differences [SMD]=0.15) and attenuated decline rates (SMD=0.18). As the meta-analysis demonstrated that ERAs do not significantly increase oedema or heart failure incidence despite modest brain natriuretic peptide elevation and weight gain, the study provides critical safety reassurance for clinical adoption.
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According to GlobalData’s Drugs Database, seven ERAs are currently in active development for chronic kidney disease and diabetic nephropathy. The meta-analysis strengthens the commercial case for broader ERA indication expansion beyond IgA nephropathy into diabetic kidney disease.
