Abstract: TH-PO0704
Complement Factor D, but Not Factor B, Correlates with Kidney Function in Glomerular Diseases
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Schubart Wellensiek, Anna S., Novartis Pharma AG, Basel, BS, Switzerland
- Hoxha, Elion, Department of Internal Medicine I, Division of Nephrology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany
- Grioni, Andrea, Novartis Pharma AG, Basel, BS, Switzerland
- Valéaux, Stéphanie, Novartis Pharma AG, Basel, BS, Switzerland
Background
Overactivation of the alternative complement pathway (AP) has been reported in many kidney diseases, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G) and idiopathic membranous nephropathy (iMN). Complement Factor B (FB) and Factor D (FD) are critical serine proteases for AP activity. High plasma FD levels have been described in patients with kidney diseases in studies with small sample sizes (consistent with the finding that FD is primarily cleared from the bloodstream through the kidneys), but blood levels of FB in these diseases are largely unknown. Here, we describe the relationship between markers of kidney function such as eGFR, serum creatinine (SCr) and proteinuria with plasma FB and FD levels in patients with IgAN, C3G and iMN.
Methods
Baseline EDTA plasma samples were collected from patients with IgAN (For FB levels, n=46; FD levels, n=22) and C3G (For FB levels, n=27; FD levels, n=17) enrolled in Phase 2 studies (NCT03373461 and NCT03832114, respectively). Longitudinal serum samples (n=503) collected from 20 patients with iMN in 3-month intervals were obtained retrospectively. FB and FD levels in serum and plasma were quantified by ELISA. Data were analyzed using Spearman’s correlation using GraphPad PRISM.
Results
FB levels did not correlate with SCr (IgAN, r=0.188; C3G, r=−0.096; iMN, r=−0.022) or eGFR (IgAN, r=−0.295; C3G, r=0.148, iMN, r=0.071). A strong correlation was observed in all diseases between FD levels and SCr (r=0.716, 0.892 and 0.803) and eGFR (r= −0.911, −0.953 and −0.860) for IgAN, C3G and iMN, respectively. Neither of the factors clearly correlated with proteinuria or phospholipase A2 receptor antibody levels in the iMN samples.
Conclusion
While no clinically relevant correlation was observed for FB levels and kidney function, this study confirms a strong, inverse correlation of FD levels and kidney function. This increase in FD levels in patients with impaired kidney function presents a potential challenge in optimizing a dosage for drugs targeting FD in kidney diseases.