Sayna Norouzi, MD

In the closing discussion, the panel looks ahead to how IgA nephropathy treatment may continue to evolve.

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

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

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

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.

In this segment, the panel discusses how monitoring strategies will need to adapt as B-cell–targeted therapies such as atacicept, sibeprenlimab, and povetacicept move into broader clinical use.

In this segment, the panel reviews the emerging clinical data for two additional BAFF/APRIL–pathway inhibitors: sibeprenlimab and povetacicept.

This segment centers on the clinical development of atacicept, a BAFF/APRIL–pathway inhibitor designed to reduce the upstream production of galactose-deficient IgA1.

In this segment, the panel compares different disease-modifying therapeutic strategies under investigation for IgA nephropathy.

In this segment, the panel discusses how the treatment landscape for IgA nephropathy is evolving with the introduction of disease-targeted therapies.

The panel examines drug classes targeting the BAFF and APRIL pathways, which play key roles in the production and regulation of IgA-secreting plasma cells.

This episode focuses on the underlying biology of IgA nephropathy, particularly the “multi-hit hypothesis.”

In this segment, the panel focuses on what “optimized supportive care” truly means for patients with IgA nephropathy.

The panel discusses how clinicians assess progression in IgA nephropathy and the importance of recognizing high-risk patients early. They emphasize that proteinuria is a central prognostic marker, and that achieving sustained reduction is critical. However, they note that ongoing eGFR decline, even when proteinuria appears improved, signals continued immune-mediated injury and should prompt re-evaluation. The group then addresses diagnostic challenges, including the fact that many patients first present after significant kidney damage has already occurred. To improve early detection, they support lowering the biopsy threshold to persistent proteinuria around 0.5 g/day, particularly when accompanied by hematuria. Increased awareness among primary care clinicians is highlighted as essential for earlier referral. Finally, the discussion includes the role of the RaDaR Registry, which collects long-term real-world data to help identify progression patterns and refine risk stratification. Overall, the segment underscores the need for early diagnosis and vigilant monitoring.

In this segment, the panelists discuss IgA Nephropathy, a glomerular disease primarily affecting young adults in their 20s and 30s. The condition has a slight predilection for males and Southeast Asians. Patients typically present asymptomatically with blood or protein in urine, or with gross hematuria following a respiratory tract infection. Less commonly, patients may develop severe nephrotic syndrome. Clinicians are most concerned with proteinuria and kidney function. Patients with proteinuria exceeding 0.5 grams are considered at risk for disease progression. The panel emphasizes that diagnoses often occur too late, with patients already having lost nearly half their kidney function. This is particularly critical because these young patients have decades ahead of them, and even small annual kidney function losses can lead to end-stage kidney disease, potentially requiring dialysis. The early detection and monitoring of these patients are crucial for preserving long-term kidney health.

C3G treatment options expand with FDA approvals of pegcetacoplan and iptacopan, offering new hope for patient care.

Panelists discuss how the complexity of diagnosing C3 glomerulopathy (C3G), the need for long-term treatment options, and the importance of addressing unmet needs, including the psychological impact on patients and families, highlights the challenges and future directions in improving care for these individuals.

Panelists discuss how patient history, vaccination status, and risk of infection influence the decision to administer complement inhibitors, with some expressing caution in high-risk cases, particularly in pediatric populations with prior infections or low immunoglobulin levels.

Panelists discuss how future clinical trials for C3 glomerulopathy (C3G) and other rare kidney diseases must evolve to accommodate emerging therapies targeting the complement system, improve inclusivity across patient populations, utilize molecular and genetic data, and reassess end point criteria to overcome challenges in patient recruitment and demonstrate treatment efficacy.

Panelists discuss how early protocol biopsies and proactive monitoring post-transplant can reveal subclinical recurrence of C3 glomerulopathy (C3G), prompting consideration of timely initiation of complement-targeting therapies to preserve graft function.

Panelists discuss how the long-term use and potential discontinuation of new complement inhibitors in C3 glomerulopathy (C3G), remain uncertain, emphasizing the need for individualized approaches, careful monitoring, and future data to guide decisions.

Panelists discuss how the APPEAR-C3G trial demonstrated that iptacopan significantly reduced proteinuria by 35% at 6 months, was well tolerated with no new safety signals over 12 months, slowed glomerular filtration rate (GFR) decline, and showed a statistically significant reduction in glomerular C3 deposit scores, though detailed biopsy clearance rates were not reported.

Panelists discuss how Jonathan Barratt, MBChB, PhD, FRCP, outlined the APPEAR-C3G study design, which featured a 6-month randomized period followed by an open-label extension, with primary end points including changes in proteinuria, glomerular filtration rate (GFR), and kidney biopsy features, emphasizing the study’s alignment with FDA guidance for ultrarare diseases.

Panelists discuss how Andrew S. Bomback, MD, MPH, having been closely involved in the VALIANT trial, outlines the study’s design—a 6-month placebo-controlled period followed by open-label treatment—and highlights its significant outcomes, including over 65% proteinuria reduction, statistically significant glomerular filtration rate (GFR) improvements, and remarkable C3 clearance on kidney biopsies.

Panelists discuss how the recent FDA approval of iptacopan marks a turning point in C3 glomerulopathy (C3G) treatment, with experts anticipating pegcetacoplan as the next likely candidate for approval due to promising phase 3 trial results and its transformative potential in patient outcomes.

Panelists discuss how the evolving availability of FDA-approved medications for C3 glomerulopathy (C3G) is reshaping clinical trial design, patient enrollment, and global access, highlighting both ethical challenges and opportunities for continued research.

Panelists discuss how physicians determine when to escalate from conservative management to complement inhibitor therapy in patients with C3 glomerulopathy (C3G), considering factors like proteinuria levels, hematuria persistence, biopsy activity scores, and the critical need for improved diagnostic capabilities to guide targeted treatment selection.

Panelists discuss how improved understanding of C3 glomerulopathy (C3G) pathobiology has led to multiple clinical trials targeting complement pathways, with considerations for efficacy measurement through proteinuria reduction and kidney biopsies, while emphasizing the importance of vaccination and patient education to manage safety concerns associated with complement inhibitors.

Panelists discuss how educating physicians and patients about C3 glomerulopathy (C3G) presents unique challenges due to its rarity, complexity, and the critical role of renal pathologists in diagnosis while emphasizing the growing importance of understanding the complement system as new targeted therapies emerge.

Panelists discuss how eculizumab initially provides short-term benefits for patients with C3 glomerulopathy (C3G) through C5a inhibition and anti-inflammatory effects but often loses efficacy over time as the disease progresses due to inadequate control at the C3 convertase level, suggesting newer complement-targeting therapies may offer better long-term management than C5 blockade.