How the 2025 KDIGO Guidelines Are Personalizing IgA Nephropathy Care, With Gerald Appel, MD

The 2025 Clinical Practice Guideline for the Management of IgA nephropathy (IgAN) and IgA vasculitis (IgAV), in tandem with the evolving therapeutic landscape, has introduced significant changes to clinical care, essentially individualizing treatment strategies.1,2

These clinical shifts included a reassessment of treatment targets for key biomarkers and a greater emphasis on addressing the underlying mechanisms driving disease progression.1

From a clinician's perspective, Gerald Appel, MD, professor of clinical medicine at Columbia University, IgAN has shifted management toward a more personalized approach, supported by a broader range of therapeutic options, combination strategies, and long-term patient-centered goals.1

In practice, this personalization is increasingly guided by biopsy findings, baseline proteinuria, and patient-specific risk factors, allowing clinicians to tailor therapy based on dominant inflammatory or hemodynamic drivers of disease.1,3

“Kidney biopsy can be very helpful in this regard. If a patient has significant scarring, therapy may focus more on ACE inhibitors, ARBs, endothelin receptor antagonists, and SGLT2 inhibitors,” said Appel.” If inflammation predominates, we may target that pathway more aggressively.”

Notably, the 2025 KDIGO IgAN guideline encourages kidney biopsy in adults with suspected IgAN and proteinuria ≥0.5 g/d. This represents a shift from the 2021 guideline, which emphasized reducing proteinuria to <1 g/d.1,3

Additionally, the guideline authors underscore proteinuria as a validated surrogate marker for long-term renal outcomes, supporting both earlier diagnostic evaluation and more aggressive treatment targets. The updated guideline reduces the recommended target to <0.5 g/d, with an ideal goal of <0.3 g/d, regardless of treatment status, reflecting evidence linking persistent proteinuria to an increased lifetime risk of kidney failure.1,2

A major new concept in the 2025 guideline is to initiate treatment with therapies to prevent or reduce pathogenic IgA production and IgA/IgA and IgA/IgG immune complex formation, along with therapies to manage the consequences of existing IgAN-induced nephron loss.1,3

“For example, targeted-release budesonide (Tarpeyo) acts on the distal ileum, specifically the Peyer’s patches, where it reduces the production of galactose-deficient IgA1 and immune complexes. This, in turn, reduces proteinuria and kidney injury,” explained Appel. “Other emerging agents also block the production of galactose-deficient IgA1 and immune complexes, while some newer therapies primarily focus on reducing proteinuria and inflammation. We now have multiple points of intervention to alter the course of the disease, and KDIGO highlights this approach.”

The 2025 KDIGO recommendations emerge amid a rapidly evolving IgAN therapeutic landscape, with 10 agents in late-phase clinical development demonstrating comparable proteinuria reductions. These late-phase programs span multiple mechanistic classes, including endothelin pathway inhibition, complement modulation, and targeted immunosuppression, reinforcing the guideline’s emphasis on combination and mechanism-driven therapy.1,2

Collectively, these advances have the potential to expand clinician choice and create new opportunities to individualize disease management.1,2

As therapeutic options continue to expand, the 2025 KDIGO guideline provides a framework for integrating emerging agents into individualized treatment strategies aimed at delaying or preventing kidney failure.1

Editor’s Note: Appel reports relevant disclosures with Novartis, Travere Therapeutics, and others.

References

1. Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney International. 2025;108(4):548-554. doi:https://doi.org/10.1016/j.kint.2025.04.003

2. Jürgen Floege, MD. PREVAIL: Felzartamab’s Sustained Clinical Outcomes In IgAN, With Jurgen Floege, MD. HCPlive. Published online November 20, 2025. doi:https://doi.org/10.1016/S0140%E2%80%916736(23)02302%E2%80%914

3. Brooks A. KDIGO Releases Updated IgA Nephropathy, IgA Vasculitis Clinical Practice Guideline. HCPLive. Published September 18, 2025. Accessed February 5, 2026. https://www.hcplive.com/view/kdigo-releases-updated-iga-nephropathy-iga-vasculitis-clinical-practice-guideline