MSN Ignite Session 5 : Optimizing Outcomes in IgAN: From Proteinuria Reduction to Novel Pathway Modulation

This topic will discuss the central role of proteinuria as the strongest modifiable predictor of disease progression in IgAN. The presentation will review evidence from registry data, retrospective cohorts, and meta‑analyses showing that greater reductions in urine protein excretion are consistently associated with slower decline in kidney function, supporting proteinuria reduction as a validated surrogate marker of long‑term renal outcome. The session will also highlight key recommendations from the KDIGO 2025 Clinical Practice Guideline, including a treat‑to‑target approach aiming for proteinuria below 0.5 g/day, and ideally 0.3 g/day or lower. Emphasis will be placed on dynamic risk assessment, timely treatment escalation, and the importance of early on‑treatment proteinuria response as a practical predictor of long‑term benefit.

This topic will address the ongoing challenge of residual risk in IgAN despite optimised supportive care, including RAAS blockade and SGLT2 inhibition. The talk will focus on the endothelin‑1/endothelin A receptor pathway as an important contributor to persistent proteinuria, glomerular injury, inflammation, and fibrosis. Clinical trial evidence and meta‑analyses supporting the proteinuria‑lowering effects of endothelin receptor antagonists will be reviewed. Building on the treat‑to‑target framework introduced in Topic 1, this presentation will examine the emerging role of multi‑pathway therapy in IgAN and discuss how updates from the KDIGO 2025 guideline support a broader therapeutic strategy to address residual risk and improve long‑term kidney outcomes.