IgAN Risk, Proteinuria Targets, and KDIGO Updates, With Chee Kay Cheung, MBChB, PhD

The management of IgA nephropathy (IgAN) is undergoing a rapid transformation, driven by a wave of emerging therapies and a deeper understanding of disease progression.

Historically, treatment strategies were constrained by limited options and an imprecise ability to identify which patients were most at risk for kidney decline. The latest update from Kidney Disease: Improving Global Outcomes (KDIGO) reflects a significant shift that moves the field toward more nuanced risk stratification, lower treatment targets, and a growing emphasis on targeted and combination therapies.

In an interview with HCPLive at the World Congress of Nephrology (WCN) Conference in Yokohama, Japan, Chee Kay Cheung, MBChB, PhD, a consultant nephrologist and honorary associate professor at the University of Leicester, noted that one of the most important gaps in prior guidance was the lack of clarity around high-risk patients, with earlier definitions relying heavily on persistent proteinuria despite renin-angiotensin system inhibition.

“Now we have very much an expanding treatment landscape with the development of new targeted therapies for IgA nephropathy… which has meant that the guidelines have had to be revised and continue to be revised to accommodate these exciting developments,” he said.

Risk assessment has also evolved. Cheung points to the IgAN prediction tool as a valuable resource for estimating short- to medium-term risk—up to 7 years—based on large patient cohorts. However, he emphasizes that this falls short of capturing the lifelong trajectory of a disease often diagnosed in patients in their 30s or 40s. As a result, he highlights the need for improved tools that can better predict long-term outcomes and guide therapeutic decision-making.

One of the most notable changes in the updated guidance is a shift in proteinuria targets. Drawing on data from international registries, Cheung notes that even patients with proteinuria between 0.5 and 1 gram per day face a meaningful risk of progression, with approximately 30% advancing to kidney failure within a decade. In response, the guidelines now advocate for reducing proteinuria as much as possible, ideally < 0.3 grams per day.

Cheung also underscores the guideline’s new framework, which categorizes therapies into those targeting upstream immune mechanisms and those addressing downstream consequences of kidney injury. Despite this progress, he stresses that evidence supporting combination approaches remains limited. Determining how best to combine or sequence therapies and ensuring access to these treatments represents a critical unmet need.

Looking ahead, Cheung describes an increasingly complex but promising therapeutic landscape. With additional agents entering clinical use and evolving guidance on their placement, he emphasizes that optimizing treatment strategies will be central to improving long-term outcomes for patients with IgAN.

“I think it's a very exciting time in IgA nephropathy, and there are more treatments coming. These all look very promising in terms of tolerability, in terms of efficacy, and where we place these treatments is going to be a key question in the future as well.”

Editors’ Note: Relevant disclosures for Cheung include Travere Therapeutics, Alexion, Alpine Immune Sciences, Calliditas Therapeutics, CSL Vifor, Novartis, Otsuka Pharmaceutical, Roche, Vera Therapeutics, and others.

References

Brooks A. KDIGO Releases Updated IgA Nephropathy, IgA Vasculitis Clinical Practice Guideline. HCPLive. September 18, 2025. Accessed March 28, 2026. https://www.hcplive.com/view/kdigo-releases-updated-iga-nephropathy-iga-vasculitis-clinical-practice-guideline