Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors: Placebo-Controlled, Crossover Trial.
Hiddo J L Heerspink, Irene L Noronha, Jose Luis Górriz et al.
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In 30 seconds
This randomized, double-blind, placebo-controlled crossover trial evaluated atrasentan added to stable renin-angiotensin system and SGLT2 inhibitor therapy in adults with IgA nephropathy, eGFR ≥30 ml/min per 1.73 m², and urinary protein >0.5 g/d. Among 54 participants, atrasentan 0.75 mg once daily reduced urinary protein-to-creatinine ratio (UPCR) relative to placebo at week 12: the difference in geometric mean percentage change was -25.3% (95% confidence interval, -36.8 to -11.7; P < 0.001). Atrasentan was reported as well tolerated, with no new safety signals.
Key findings
- At week 12, the UPCR treatment difference for atrasentan versus placebo was -25.3% (95% confidence interval, -36.8 to -11.7; P < 0.001).
- During treatment period 2 at week 24, the UPCR treatment difference was -26.4% (95% confidence interval, -45.8 to -0.0).
- One unrelated serious adverse event occurred; fluid retention events were uncommon and none required hospitalization.
- There were no treatment-related adverse-event discontinuations or deaths.
Why it matters
Proteinuria can persist in IgA nephropathy despite renin-angiotensin system and SGLT2 inhibition. This trial provides controlled evidence that adding atrasentan can further reduce proteinuria in adults receiving both therapies, while reporting few serious safety concerns during the study. The result informs assessment of an additional treatment option, although proteinuria reduction is the reported outcome.
What to keep in mind
The crossover study assessed UPCR over 12-week treatment periods; the abstract does not report longer-term kidney outcomes.