Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors Placebo-Controlled, Crossover Trial
Background Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:dnet:incliva_____::a813e6e41d8d20efd80d326443803b40 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/20824 |
| Access Level: | acceso abierto |
| Palabra clave: | CKD clinical nephrology clinical trial glomerular disease GN IgA nephropathy kidney disease proteinuria SGLT2 inhibitors |
| Sumario: | Background Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of atrasentan has not been rigorously determined. Methods We performed a randomized, double-blind, placebo-controlled crossover study of atrasentan in adults with IgA nephropathy, eGFR >= 30 ml/min per 1.73 m(2), and urinary protein >0.5 g/d while on maximal, stable RASi and SGLT2i. Participants were randomized 1:1 to either sequence AB or sequence BA (0.75 mg atrasentan [A] once daily during period 1 and matching placebo [B] during period 2 or vice versa), with a 12-week washout period in between. The primary end point was the change in urinary protein-to-creatinine ratio (UPCR) to week 12. The secondary end point was the change in UPCR to week 24. Safety end points included the type, incidence, severity, seriousness, and relatedness of adverse events (AEs). Results We recruited 54 participants with mean age 48 years (SD 12), 43% female, mean eGFR 63 ml/min per 1.73 m(2) (SD 22), and median UPCR 1.0 g/g (Q1-Q3, 0.7-1.4). Treatment with atrasentan versus placebo resulted in a difference in geometric mean percentage change in UPCR at week 12 of -25.3% (95% confidence interval, -36.8 to -11.7; P < 0.001). The treatment difference in UPCR between atrasentan versus placebo during treatment period 2 at week 24 was -26.4% (95% confidence interval, -45.8 to -0.0). There was one unrelated serious adverse event. Fluid retention events were uncommon, and none required hospitalization. There were no study drug discontinuations due to treatment-related adverse events and no deaths. Conclusions Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy and proteinuria >= 0.5 g/d treated with RASi and SGLT2i therapy. Atrasentan was well tolerated, and no new safety signals emerged. |
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