Abstract: FR-PO0933
Pegcetacoplan Rescue After Urinary Loss of C5 Inhibitors in a Pediatric Patient with C3 Glomerulopathy
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Koka, Niharika, Ascension Texas, Austin, Texas, United States
- Redding, Mersady, Ascension Texas, Austin, Texas, United States
- Mecci, Nazia, Ascension Texas, Austin, Texas, United States
Introduction
C3 glomerulopathy (C3G) is a rare complement-mediated kidney disease, with up to 50% progressing to renal failure within 10 years. Pegcetacoplan, a C3/C3b inhibitor FDA-approved for C3G in patients ≥12 years, offers proximal complement blockade. We report rescue therapy with pegcetacoplan after failure of C5 inhibitors from urinary drug losses.
Case Description
An 8-year-old male presented with pneumonia, Streptococcus pneumoniae bacteremia, and acute kidney injury requiring continuous renal replacement therapy. Evaluation revealed nephrotic-range proteinuria (UPC 14.1 g/g), hypocomplementemia (C3 11 mg/dL), absent AH50, low factor B/H, and elevated sC5b-9 (545 ng/mL). Biopsy showed diffuse proliferative glomerulonephritis with 65% crescents. Genetic testing identified homozygous MCP/CD46 and CFH-H3 risk haplotypes.
After pulse methylprednisolone and cyclophosphamide, renal function recovered but nephrotic syndrome persisted. Ravulizumab was initiated; pharmacokinetic studies revealed subtherapeutic levels (5 mcg/mL; goal >175) with elevated sC5b-9, indicating urinary drug loss. Dose intensification, tacrolimus, and ACEi provided minimal improvement. Eculizumab every 2 weeks also failed (UPC 11–17 g/g, albumin 1.4–1.8 g/dL).
At age 12, subcutaneous pegcetacoplan was started twice weekly. Within 3 months: albumin rose from 1.6 to 3.6 g/dL, UPC fell from 17.8 to 3.5 g/g (80% reduction), and sC5b-9 normalized. At 12 months, albumin remains 2.6–3.0 g/dL with UPC 2–6 g/g and stable renal function.
Discussion
This case highlights urinary drug loss as an underrecognized mechanism of complement inhibitor failure in nephrotic patients. Pharmacokinetic monitoring identified this mechanism and should be considered when response is inadequate. Pegcetacoplan's success likely reflects proximal C3 blockade and subcutaneous dosing reducing dependence on serum levels vulnerable to urinary losses. Early transition to C3 inhibition should be considered over prolonged C5 inhibitor escalation in patients with persistent nephrotic proteinuria.
Acknowledgment
ChatGPT (OpenAI, GPT-4o model, OpenAI, San Francisco, CA, USA) was used on May 9, 2026, to assist in refinement of the schematic figure. The authors reviewed and take full responsibility for all content.