Successful Treatment of Refractory Immune Complex-Mediated Membranoproliferative Glomerulonephritis with Pegcetacoplan: A Case Report.

Abstract

Immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) lacks proven targeted therapy and is often refractory to nonspecific immunosuppression. Dysregulation of the alternative complement pathway provides a mechanistic rationale for proximal C3 inhibition. This article presents our experience with the management of a case of refractory IC-MPGN with the C3 inhibitor, pegcetacoplan. A 19-year-old man presented with nephrotic-range proteinuria, haematuria, hypoalbuminaemia (20 g/L), and depressed complement (C3 0.06-0.14 g/L with normal C4). Kidney biopsy demonstrated IC-MPGN with granular IgA/IgG/C3 along capillary loops and electron-dense deposits in subendothelial, intramembranous, and subepithelial locations. Despite treatment with corticosteroids and tacrolimus, disease activity persisted, prompting initiation of pegcetacoplan 1,080 mg subcutaneously twice weekly. The urine protein-creatinine ratio (UPCR) decreased to 751 mg/g (-70% from baseline), and 24-h urinary protein excretion declined to 1,386 mg/day (-83%). Serum albumin increased from 20 to 36 g/L, while serum creatinine remained stable (92 µmol/L). Complement levels normalised, with C3 rising from 0.06 g/L to 1.27 g/L, permitting discontinuation of antihypertensive and immunosuppressive medications. No adverse events were observed. This case supports C3-targeted therapy with pegcetacoplan to achieve rapid biochemical and clinical remission in refractory IC-MPGN. Longer follow-up with histologic correlation and biomarker-guided selection is needed to define durability and responders.