Abstract: SA-PO0733
B-Cell-Depleting Therapies in C3 Glomerulopathy and Primary Immune-Complex Membranoproliferative Glomerulonephritis as a Treatment Option
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Gunkel, Maja, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Kuehne, Lucas, Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Kolbrink, Benedikt, Department of Nephrology and Hypertension, University Hospital Schleswig, Holstein-Campus Kiel, Kiel, Germany
- Zotta, Federica, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- Vivarelli, Marina, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- Schmitt, Roland, Department of Nephrology and Hypertension, University Hospital Schleswig, Holstein-Campus Kiel, Kiel, Germany
- Brinkkoetter, Paul T., Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Huber, Tobias B., III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Freiwald, Tilo, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Introduction
C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (pIC-MPGN) are rare kidney diseases with a strong case for complement dysregulation as the main pathological factor. However, with only approximately half of the patients responding to complement inhibition, questions of patient subgroups and alternative treatment strategies are prompted. Anti-complement autoantibodies such as nephritic factors and anti-factor H antibodies are commonly found in both C3 glomerulopathy and pIC-MPGN, but their functional role in pathogenesis is debated and their detection remains challenging. B cell-depleting strategies offer to deplete these autoantibodies and thus offer a more causal treatment strategy as opposed to inhibiting the resulting complement activation.
Case Description
We have conducted a multi-center, retrospective case series of 8 C3G/pIC-MPGN patients treated with rituximab (RTX) from 2015 to 2025. Baseline characteristics included age (mean 40.4 +/-19.3 years), sex (6 female, 2 male), proteinuria at baseline (2.77 +/-2.82 g/g), baseline C3 (65.7 +/-61.1 mg/dl), presence of autoantibodies (C3 Nephritic Factor n=4, Factor H autoantibody n=3, containing 1 double positive). Proteinuria (mg/g) and serum creatinine (mg/dl) were analyzed at baseline and 3, 6, 9 and 12 months after RTX as primary outcome parameters.
We identified a mean reduction of proteinuria by 33.6% at 6 months (p=0.163, n=8), 61.8% at 9 months (p=0.055, n=8) and 18.2% at 12 months (p=0.344, n=6, one-sided Wilcoxon Test). The mean reduction of serum creatinine was 7% after 6 months (p=0.680), 4% after 9 months (p=0.371) and 9% after 12 months (p=0.606). The average cumulative RTX dose was 1.93 g during the observation. There were no deaths and no initiation of renal replacement therapy.
Discussion
In this retrospective multi-center cohort of 8 C3G/pIC-MPGN patients treated with RTX, we observed a clinically relevant but statistically inconclusive transient reduction in proteinuria and serum creatinine during follow-up. Given the small sample size larger prospective studies are needed to better characterize the renal response. With the expanding landscape of B cell directed therapies, antibody depletion in C3G and pIC-MPGN warrants renewed investigation as a potential therapeutic strategy.