Pegcetacoplan in idiopathic and familial pediatric C3 glomerulopathy

Abstract Background C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) represent a continuous spectrum of a glomerular disease driven by dysregulation of the complement and characterized by C3 deposition alone or associated with immunoglobulins. Despite the significant burden and poor prognosis associated with these conditions, no therapies have been approved for their treatment in children. Methods In this observational study, we present three pediatric cases that span the clinical and pathogenic spectrum of C3G/IC-MPGN, including multi-resistant nephrotic syndrome with clear terminal pathway activation, familial genetic C3G with early anti-C3 intervention, and multi-resistant nephrotic syndrome of unclear etiology, likely related to IC. Results All three patients were successfully treated with the C3/C3b inhibitor pegcetacoplan, that inhibited C3, blocked C3 consumption, and restored physiological C3 levels, leading to significant proteinuria reduction within the first month. After six months, patients experienced notable improvements in kidney function, a complete remission of nephrotic syndrome, and normalized proteinuria levels. There were no treatment-related adverse events, only mild infections that resolved with standard oral therapy. Conclusions These findings support the potential of C3 inhibition with pegcetacoplan in pediatric patients with refractory or genetic C3G. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.