Pegcetacoplan in idiopathic and familial pediatric C3 glomerulopathy

TL;DR

This study shows that pegcetacoplan, a C3 inhibitor, effectively treats pediatric C3 glomerulopathy, improving kidney function and reducing proteinuria without serious side effects.

Contribution

The study presents the first pediatric cases successfully treated with pegcetacoplan for C3 glomerulopathy.

Findings

Pegcetacoplan significantly reduced proteinuria within one month in all three pediatric patients.

After six months, patients showed improved kidney function and remission of nephrotic syndrome.

Treatment was well-tolerated with no serious adverse events reported.

Abstract

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.

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.

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.

These findings support the potential of C3 inhibition with pegcetacoplan in pediatric patients with refractory or genetic C3G.

A higher resolution version of the Graphical abstract is available as Supplementary information.

The online version contains supplementary material available at 10.1007/s00467-025-07092-7.

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