Rethinking When and How to Treat IgA Nephropathy, With Sayna Norouzi, MD

The treatment landscape for IgA nephropathy is undergoing a profound transformation, driven by updated clinical guidelines, earlier diagnosis, and a rapidly expanding therapeutic arsenal. Where management was once largely reactive, the field is now moving toward earlier, more aggressive, and more targeted intervention aimed at altering disease trajectory.

In an interview with HCPLive at World Congress of Nephrology in Yokohama, Japan, Sayna Norouzi, MD, a clinical nephrologist and associate professor of medicine at Loma Linda University Medical Center, said one of the most significant shifts between the 2021 and 2025 guidelines is the redefinition of high-risk disease.

Previously, proteinuria thresholds of around 1 gram per day were used to guide treatment escalation. Now, patients with proteinuria ≥0.5 g/day are considered at risk, representing a major change in how clinicians identify and manage disease severity. This lower threshold underscores a growing recognition that IgA nephropathy is not a benign condition and can lead to kidney failure if not addressed early.

“The sooner you diagnose these patients, [the sooner] you're going to be able to treat them, and with effective treatment of IgA nephropathy, you might be able to delay dialysis or transplant or complications in general, for your patients,” she said.

The updated guidelines also emphasize more ambitious treatment goals, with a target proteinuria level ideally < 0.3 g/day. Norouzi explains that this shift reflects mounting evidence linking lower proteinuria to improved long-term outcomes, including delayed progression to dialysis or transplant. As a result, clinicians are now encouraged to pursue tighter disease control from the outset.

Another key evolution lies in treatment strategy. Historically, care began with supportive measures like blood pressure control, lifestyle modification, and initiation of RAAS blockade, with additional therapies introduced only after inadequate response. In contrast, the 2025 guidance promotes a more proactive, simultaneous approach, and while supportive care remains foundational, clinicians are now urged to initiate therapies targeting the underlying pathophysiology earlier in the disease course rather than waiting for treatment failure.

This paradigm shift is enabled by a growing list of therapeutic options. Norouzi highlights the emergence of targeted agents, including targeted-release budesonide, endothelin receptor antagonists like sparsentan and atrasentan, complement inhibitors such as iptacopan, and newer APRIL-targeting therapies. Together, these agents provide clinicians with multiple avenues to reduce proteinuria and preserve kidney function.

Despite this progress, she says important questions remain. Norouzi notes that clinical trials provide only a limited snapshot of efficacy and safety, often over relatively short durations. As these therapies enter real-world practice, she says clinicians will need to better understand long-term tolerability, optimal sequencing, and effectiveness in more heterogeneous patient populations.

“We need more data on these medications, on the safety, on how they are going to work over time. The clinical trials are looking at a limited amount of time. They follow patients for 9 months for the initial outcome data, and then they follow patients for 2 years,” Norouzi said. “Once the medication is FDA approved and it's on the market, that's when we are going to have more information and see in real life if patients are tolerating the medications. We're going to hear more about the side effects, how to monitor these patients over time, and if they are responding well to the medications as well.”

Editors’ note: Norouzi reports relevant disclosures with Calliditas, Travere, Apellis and others.

References

1. 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

2. Campbell P. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. August 7, 2024. Accessed April 1, 2026. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy

3. Campbell P. Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy. April 2, 2025. Accessed April 1, 2026. https://www.hcplive.com/view/atrasentan-vanrafia-receives-accelerated-approval-in-igan