Editorial disclosure: This article is original educational commentary based on the cited literature. It summarizes and interprets published evidence rather than reproducing source text. Clinical decisions should be based on the full original publications, current guidelines, regulatory status, and individual patient factors.
A rapidly changing therapeutic field
IgA nephropathy has moved from limited disease-modifying options into one of the most active areas of therapeutic development. Treatment increasingly combines reduction of proteinuria, preservation of filtration and modification of disease-specific pathways.
What ALIGN contributes
Long-term results from the phase 3 ALIGN trial provide evidence for atrasentan, a selective endothelin A receptor antagonist. In the reported analysis, eGFR declined by 7.5 mL/min/1.73 m² with atrasentan versus 9.9 mL/min/1.73 m² with placebo. The between-group difference was 2.4 mL/min/1.73 m², but the reported P value of 0.057 did not reach conventional statistical significance.
Endothelin signaling contributes to vasoconstriction, inflammation and fibrotic signaling, making receptor blockade an attractive non-immunosuppressive strategy in proteinuric disease.
Combination therapy needs evidence
Supportive care remains foundational, including blood-pressure control, renin–angiotensin system blockade when indicated, proteinuria reduction and appropriate SGLT2 inhibition. Additional therapies should be selected according to residual risk, disease activity, kidney function and patient preferences. Individual agents should not be assumed to have additive benefit simply because they work in isolation.
Key clinical takeaways
- Atrasentan provides additional long-term evidence in IgA nephropathy.
- The reported ALIGN eGFR difference did not reach conventional statistical significance.
- Combination therapy should be evidence-based rather than assumed.
References
- Heerspink HJL, et al. Atrasentan in patients with IgA nephropathy (ALIGN): final 2.5-year results. Lancet. 2026;407:2387–2401.
- Wang M. Long-term kidney protection in IgA nephropathy with atrasentan. Nat Rev Nephrol. 2026;22:520. DOI.