Abstract: SA-PO0737
C3 Glomerulonephritis with High PR3 Titer Successfully Treated with Pegcetacoplan
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
- Moseley, Allen Kai, Ochsner Health, New Orleans, Louisiana, United States
- Shueib, Ali, Ochsner Health, New Orleans, Louisiana, United States
- Velez, Juan Carlos Q., Ochsner Health, New Orleans, Louisiana, United States
- Asad, Maira, Ochsner Health, New Orleans, Louisiana, United States
- Ogundipe, Ayomide, Ochsner Health, New Orleans, Louisiana, United States
Introduction
C3 glomerulonephritis (C3GN) is a rare complement mediated disease driven by alternative pathway dysregulation. Although ANCA-associated vasculitis (AAV) may rarely involve C3 deposition, a serology-pathology mismatch - where PR3 is positive but pathology shows C3GN rather than pauci-immune necrotizing GN - is rare. This case highlights the necessity of kidney biopsy to decouple serology from pathology to guide targeted therapy
Case Description
A 33-year-old man presented with fatigue, lower extremity edema, and hematuria. Labs revealed acute kidney injury (serum Cr 2.67 mg/dL, eGFR 31 mL/min/1.73m2), subnephrotic range proteinuria (UPCR 0.66 g/g), and anemia (Hgb 7.5 g/dL). Urinary sediment microscopy revealed RBC casts and WBC casts. Serologic workup was significant for elevated PR3-ANCA (>8 U/mL) and low C3 (<11 mg/dL) with normal C4. Due to suspicion for AAV, pulse dose steroids were started. A kidney biopsy was performed. Light microscopy showed a diffuse membranoproliferative pattern. Immunofluorescence revealed dominant C3 staining inconsistent with AAV. Electron microscopy confirmed mesangial and subendothelial electron dense deposits. Further specialized testing identified complement factor H (CFH) serum autoantibodies. Infectious (including endocarditis) and malignancy workup were negative. Upon confirming C3GN driven by CFH autoantibodies, steroids were tapered. Following vaccinations for encapsulated organisms, the patient was initiated on the novel C3 inhibitor pegcetacoplan (1,080 mg twice weekly), bridged briefly with mycophenolate mofetil. After 1.5 months of targeted therapy, Cr improved from 2.0 to 1.0 mg/dL, serum C3 normalized, with near-complete resolution of proteinuria (UPCR 0.06), hematuria, and urinary sediment activity.
Discussion
This case highlights the importance of kidney biopsy to confirm the diagnosis of C3GN when confounding factors exist. High PR3-ANCA in C3GN has not been previously reported. In our case, it is not clear whether they reflected unusual ANCA-like autoimmunity or a laboratory cross-reactivity. Pegcetacoplan is a new FDA-approved therapeutic agent that elicits fast resolution of the cardinal features of C3GN.