Abstract: SA-PO0708
Refractory C3 Glomerulonephritis with Rapid Clinical and Biochemical Response to Pegcetacoplan After Failure of Eculizumab and Mycophenolate
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
Author
- Reyes Bahamonde, Joselyn, St. Luke's University Health Network, Bethlehem, Pennsylvania, United States
Introduction
C3 Glomerulonephritis (C3GN) is a rare complement-mediated glomerular disorder caused by dysregulation of the alternative pathway. We present a patient with C3GN refractory to terminal complement inhibitor (Eculizumab), but achieved biochemical and clinical improvement soon after C3 targeting therapy with Pegcetacoplan
Case Description
22 yo woman with hypertension, pediatric onset of C3GN presented with persistent disease despite prolonged immunosuppression with steroids, Mycophenolate, and Eculizumab. Initially diagnosed in 2015 at age 11in the setting of microhematuria and proteinuria. Kidney biopsy was consistent with C3GN. She was treated with Prednisone and Mycophenolate.
Due to recurrent flares, Eculizumab was initiated every two weeks in 2022. Despite three years of Eculizumab, the patient never achieved remission, has persistent proteinuria of 1.5 to 4 grams, hematuria, and persistent low C3 levels. Kidney function remained normal (creatinine 0.5mg/dL), and the patient was transitioned to adult nephrology care with proteinuria of 2.4mg/dL, low C3, and hematuria.
In March of 2026, therapy was changed to the C3 inhibitor, Pegecetacoplan, with discontinuation of Eculizumab. Four weeks after initiation of Pegcetacoplan, serum C3 normalized for the first time since diagnosis and increased to above-normal levels. Two months after therapy with a C3 inhibitor, proteinuria rapidly improved from 3.6 g/g to 0.6 g/g. Hematuria resolved to 2-4 RBC/hpf. (Figure 1)
Discussion
Persistent low serum C3 level during Eculizumab therapy is likely due to ongoing upstream alternative complement activation despite terminal inhibition of C5. In contrast, proximal C3 inhibition with Pegcetacoplan leads to a reduction in ongoing C3 consumption, resulting in rapid normalization of C3 and subsequently clinical improvement with reduction of proteinuria and hematuria. This case highlights the limitations of terminal complement inhibition in C3GN and supports proximal complement inhibition as a better therapeutic strategy in patients with C3GN