Abstract: SA-PO0641
Efficacy and Safety of Targeted Complement Inhibitors in C3 Glomerulopathy and Primary Immune Complex Membranoproliferative Glomerulonephritis: A Systematic Review and Meta-Analysis
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
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
- Carvalho de Alvarenga, Gabriela Sanches Vicente, Faculdade de Medicina de Jundiai, Jundiaí, São Paulo, Brazil
- Sai Sravya, S., Government Medical College Thiruvananthapuram, Nizamabad, India
- Almubarak, Obaida Mohammed Bakr, Ankara Universitesi, Ankara, Turkey
- Bertholucci, Jonatas Pereira, Hospital das Clínicas da FMRP - USP, Ribeirão Preto, Brazil
- Yathindra, Meenakshi, Roxborough Memorial Hospital School of Nursing, Philadelphia, Pennsylvania, United States
- Duque, Juan, University of Miami Miller School of Medicine, Miami, Florida, United States
Background
C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are complement-mediated kidney diseases with no approved disease-modifying therapies for most patients
Methods
PubMed, Embase, and Cochrane Library were searched for RCTs evaluating proximal or terminal complement inhibitors in patients with C3G or primary IC-MPGN. Native-kidney data were prioritized when available. Random-effects models were used and heterogeneity assessed with I^2 statistics
Results
Four RCTs (N=267) were included. The overall proteinuria analysis showed a non-significant trend toward reduction with high heterogeneity. However, a sensitivity analysis excluding the phase 2 danicopan trial due to suboptimal therapeutic exposure demonstrated significant proteinuria reduction (MD −42.04%; 95% CI −71.19 to −12.89; p=0.005; I^2=82%). This effect was greater in subgroup analyses of proximal inhibitors and native-kidney populations (MD −54.07%; 95% CI −82.17 to −25.97; p=0.0002; I^2=74%). In the primary eGFR analysis of 3 RCTs reporting absolute eGFR change, complement inhibitors significantly improved kidney function preservation (MD +3.45 mL/min/1.73 m2; 95% CI 0.38 to 6.52; p=0.03; I^2=0%). Proximal blockers also significantly increased achievement of the composite renal endpoint (RR 8.57; 95% CI 2.78 to 26.42; p=0.0002; I^2=22%). No increase in serious adverse events was observed (RR 1.14; 95% CI 0.51 to 2.58; p=0.75; I^2=0%)
Conclusion
Targeted complement inhibitors, particularly proximal blockers, significantly reduce proteinuria and improve renal outcomes in C3G and primary IC-MPGN with a favorable safety profile. These findings support upstream complement inhibition as a promising strategy in complement-mediated