#4-77E. Expanding the Arsenal: Atrasentan for Kidney Preservation in IgA Nephropathy (Lancet, 2026)

How can we further slow the progression of IgA nephropathy in patients who are already on optimized supportive care? In this episode, we delve into the final 2.5-year results of the phase 3 ALIGN trial, which evaluated the efficacy and safety of atrasentan, a selective endothelin A receptor antagonist, in patients with IgA nephropathy. The study demonstrated that atrasentan provided early and sustained reductions in proteinuria and mitigated the decline of estimated glomerular filtration rate (eGFR) over 2.5 years, while maintaining a favorable safety profile. The most crucial clinical takeaway is that atrasentan suggests a clinically meaningful preservation of kidney function even when used concomitantly with SGLT2 inhibitors, highlighting its potential as a novel non-immunosuppressive add-on therapy. However, when critically appraising this study, it is important to note that the between-group difference in eGFR change at week 136 narrowly missed statistical significance (p=0.057), and the findings regarding SGLT2 inhibitor co-administration are based on a small exploratory stratum. For practicing physicians, this paper is highly relevant as it underscores atrasentan as a promising new therapeutic option to improve long-term kidney survival in IgA nephropathy, expanding our arsenal beyond existing standard-of-care treatments.

Citation: Heerspink HJL, et al. Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2026. DOI: 10.1016/S0140-6736(26)00960-8

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.