Abstract: FR-PO0834
Effect of Selective Endothelin A Receptor Antagonists on Proteinuria in IgAN: Systematic Review and Meta-Analysis
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Sharma, Gaurav, Jaipur National University Institute of Medical Sciences and Resarch Centre, Jaipur, RJ, India
- Gutta, Durga Prasad, Siddhartha Medical College, Vijayawada, AP, India
- Pavuluri, Sai Swetha, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, OD, India
- Patel, Karma Jayeshkumar, Maulana Azad Medical College, New Delhi, DL, India
- Lanka, Nidhi, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Mumbai, MH, India
Background
IgA nephropathy (IgAN), a leading cause of chronic kidney disease, is strongly associated with persistent proteinuria, a key predictor of progression. Selective endothelin A receptor antagonists (sETARAs), including the FDA-approved atrasentan, show promise in reducing proteinuria. This meta-analysis quantifies the efficacy and safety of sETARAs in IgAN, with supporting observational evidence.
Methods
A search of PubMed, Embase, Scopus, and ClinicalTrials.gov through April 2025 identified RCTs enrolling adults with biopsy-proven IgAN comparing sETARAs to placebo on background RAS blockade and reporting proteinuria outcomes at 24–36 weeks. Exclusion criteria included pediatric/secondary IgAN, uncontrolled designs, and incomplete data.The primary outcome was the placebo-adjusted percent change in proteinuria, while peripheral edema was the key secondary outcome assessed. Risk of bias was assessed using Cochrane RoB 2.0. Meta-analysis used the generic inverse variance method with a random-effects model in RevMan 5.4 version.
Results
Two RCTs (N=336; sETARA: 167, placebo: 169) showed atrasentan (0.75mg) reduced proteinuria by 36.1% at 36 weeks (95% CI: −45.2 to −27.0), and SC0062 (20mg) by 51.6% at 24 weeks (95% CI: −66.4 to −36.8); only the 20mg arm was included for dose uniformity. Confidence intervals reflect meta-analytic estimates and may differ slightly from original trials. Pooled reduction was 42.7% (95% CI: −57.7 to −27.7; P < 0.00001) with moderate heterogeneity (I2 = 67%)(Figure 1). Peripheral edema rates were low: 8.9% vs. 6.5% (Atrasentan vs. placebo) and 3% vs. 15% (SC0062 vs. placebo). The AFFINITY study (N = 20, not pooled) showed ~45% sustained proteinuria reduction at 52 weeks.
Conclusion
Selective ETA receptor antagonists significantly lower proteinuria in IgAN. Atrasentan and SC0062 were well tolerated, with low rates of edema and no major safety signals. These results, supported by observational data, warrant further research on long-term renal outcomes and integration into treatment protocols.