C3 glomerulopathy in children: a European longitudinal study evaluating outcome

Pediatr Nephrol. 2025 Apr;40(4):979-986. doi: 10.1007/s00467-024-06587-z. Epub 2024 Nov 26.

Abstract

Background: C3 glomerulopathy is a rare clinical entity characterized by dysregulation of the alternative complement pathway in glomerular disease. Studies defining the natural history of C3G in the pediatric population are scarce.

Methods: Patients included in this retrospective study were diagnosed between 2011 and 2020 in 12 European pediatric nephrology units. Data were collected from baseline, 6 months, 12 months and at the last follow-up. Complete remission (CR) was defined as a urinary protein creatinine ratio (UPCR) < 0.3 mg/mg with normal estimated glomerular filtration rate (eGFR). Partial remission was defined as a decrease in UPCR to 0.3 and 3 mg/mg with normal eGFR. Lack of remission was defined as non-response.

Results: A total of 108 pediatric patients were included. Complete remission was achieved in 71/108 patients (65.7%), with probability of CR of 50% at 1.8 years and of 78% at 7 years. At presentation by univariate analysis the predictive factors at presentation associated with CR included eGFR (p = 0.028), UPCR (p = 0.004), serum C3 levels (p = 0.018), elevated plasma sC5b9 levels, defined as > 400 ng/ml, (p = 0.037), the presence of endocapillary proliferation (p = 0.017), and the absence of dense deposits on electron microscopy (p = 0.032). By multivariate analysis a low UPCR at presentation (p < 0.001) and the presence of endocapillary proliferation (p < 0.01) remained positively associated with CR.

Conclusions: Our data confirm that C3G has a more benign outcome in children compared to previous reports in adults, and suggest that endocapillary proliferation and the degree of proteinuria at onset are the most relevant prognostic factors.

Keywords: C3 glomerulonephritis; Children; Complement system; Dense deposit disease; Outcome.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Complement C3* / analysis
  • Complement C3* / metabolism
  • Complement Pathway, Alternative / immunology
  • Creatinine / urine
  • Europe / epidemiology
  • Female
  • Glomerular Filtration Rate
  • Glomerulonephritis* / drug therapy
  • Glomerulonephritis* / immunology
  • Glomerulonephritis, Membranoproliferative* / immunology
  • Humans
  • Infant
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Longitudinal Studies
  • Male
  • Prognosis
  • Proteinuria / urine
  • Remission Induction
  • Retrospective Studies

Substances

  • Complement C3
  • C3 protein, human
  • Creatinine