Sayna Norouzi, MD, is an assistant professor of medicine, clinical nephrologist, and founder and director of the glomerular disease and polycystic kidney disease clinics at Loma Linda University Medical Center.

Sayna Norouzi, MD

Evolving Therapeutic Strategies and Real-World Application in IgAN

This episode focuses on translating clinical evidence into everyday treatment decisions. The panel emphasizes that the expanding therapeutic landscape requires individualized care, balancing disease severity, patient comorbidities, and willingness to engage in ongoing monitoring. They discuss how clinicians might choose between targeted-release budesonide, dual endothelin/angiotensin receptor blockade (e.g., sparsentan), and B-cell modulators, depending on proteinuria level, risk of progression, and tolerance profiles. Real-world considerations such as clinic workflow, infusion vs. injection preferences, and patient adherence are highlighted. The group stresses the importance of shared decision-making, noting that treatment choices are not solely algorithmic but influenced by patient goals and lifestyle. They conclude that as more agents become available, clinicians must be prepared to sequence and adjust therapy over time, rather than relying on a single long-term intervention.

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This episode focuses on translating clinical evidence into everyday treatment decisions.

2025 KDIGO Guideline Update for IgAN

The KDIGO 2025 guidelines update emphasizes a more aggressive approach to treating IgA Nephropathy. The experts highlight key changes, including recognizing a broader range of patients as high-risk and lowering the proteinuria threshold for intervention to 500 milligrams. The guidelines now advocate for earlier biopsy and more comprehensive treatment strategies.

The panelists stress the importance of ambitious treatment goals, including reducing eGFR decline to less than one milliliter per minute per year and targeting proteinuria below 0.5 grams daily, ideally below 0.3 grams. The panel agrees that these goals were unimaginable just five years ago.

The guidelines recommend simultaneous treatment approaches, moving away from sequential therapies. They encourage targeting multiple disease mechanisms, including supportive care and immunological interventions. The experts emphasize the need to treat IgA Nephropathy as a lifelong condition, with the ultimate goal of protecting kidney function and avoiding dialysis.

The KDIGO 2025 guidelines update emphasizes a more aggressive approach to treating IgA Nephropathy.

Challenges in Integrating B-Cell Modulators into IgAN Clinical Practice

In this segment, the panel focuses on clarifying terminology and discussing evolving treatment strategies for IgA nephropathy. They agree that “supportive therapy” is a more accurate and appropriate term than “conservative therapy” when describing foundational management approaches. The discussion then turns to the potential of emerging treatments, particularly B-cell modulators, which offer the ability to more directly address the underlying pathophysiology of the disease. These therapies may reduce pathogenic GD-IgA1 production, lower hematuria and proteinuria, and help slow the decline in kidney function—key goals in IgA nephropathy management. The speakers contrast these newer mechanism-targeted options with traditional therapies like RAAS inhibitors and SGLT2 inhibitors, which provide benefit but do not directly modify the drivers of disease. Overall, the panel highlights that newer therapies represent an important advancement, offering opportunities to more effectively intervene in the biological processes central to IgA nephropathy.

In this segment, the panel focuses on clarifying terminology and discussing evolving treatment strategies for IgA nephropathy.

Positioning Emerging B-Cell Modulators in Future IgAN Treatment Algorithms

In this segment, the panel discusses how B-cell modulators such as atacicept, sibeprenlimab, and povetacicept may fit within evolving treatment pathways for IgA nephropathy. They emphasize that optimized supportive care—including maximized RAAS inhibition, SGLT2 inhibitors, blood pressure control, and dietary sodium restriction—remains foundational. However, they note that persistent proteinuria despite these measures should prompt consideration of disease-modifying therapy. The panel explains that B-cell modulators may be positioned earlier in the treatment algorithm than traditional systemic corticosteroids because they target upstream pathogenic processes rather than broadly suppressing immunity. They also discuss differentiation among agents, including dosing schedules, biomarkers used to track response, and potential safety considerations. The discussion highlights that future treatment strategies may involve pairing supportive therapy with early initiation of a B-cell modulator, rather than reserving disease-modifying treatment only for advanced or rapidly progressive disease. Overall, the panel anticipates that these agents will shift practice toward earlier, mechanism-based intervention.

In this segment, the panel discusses how B-cell modulators such as atacicept, sibeprenlimab, and povetacicept may fit within evolving treatment pathways for IgA nephropathy.

Sayna Norouzi, MD

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