Immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) lacks proven targeted therapy and is often refractory to non-specific immunosuppression. Dysregulation of the alternative complement pathway provides a mechanistic rationale for proximal C3 inhibition. A 19-year-old man presented with nephrotic-range proteinuria (24-hour protein 7,988 mg/day; urine protein–creatinine ratio UPCR 2,502 mg/g), 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. By August 2025, UPCR decreased to 751 mg/g (−70% from baseline), and 24-hour 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 and C4 improving to 0.18 g/L, permitting discontinuation of antihypertensive and immunosuppressive medications. No adverse events were observed. Pegcetacoplan achieved rapid biochemical and clinical remission in refractory IC-MPGN, enabling cessation of non-specific immunosuppression and supporting C3-targeted therapy for complement-dysregulated disease. Longer follow-up with histologic correlation and biomarker-guided selection is needed to define durability and responders.
Al-Muhaiteeb et al. (Fri,) studied this question.