Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in children and adolescents.

ABSTRACT

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerulopathy in children. Recently, a new classification based on immunohistological features has been established. Infections and anomalies in complement-regulating genes, leading to alternative complement pathway activation, are suspected to trigger the disease. Nevertheless, little is known about optimal treatment and outcome in children with immune-complex-MPGN (IC-MPGN) and C3-glomerulopathy (C3G). METHODS: The method used is retrospective analysis of clinical, histological, and genetic characteristics of 14 pediatric patients with MPGN in two medical centers. RESULTS: Mean age of the patients was 10.6 ± 4.5 years. Patients were grouped into C3G (n = 6) and IC-MPGN (n = 8). One patient showed a likely pathogenic variant in the CFHR5 gene. All 10 patients had risk polymorphisms in complement-regulating genes. Most patients were treated with ACE inhibition, steroids, and mycophenolate mofetil. Three patients with C3G received eculizumab. Median follow-up was 2.3 years. After 1 year of disease, three patients (two C3G, one IC-MPGN) reached complete, five patients partial (three IC-MPGN, two C3G), and five patients no remission (four IC-MPGN, one C3G). One patient progressed to end-stage renal disease (ESRD) 6 years after disease onset. CONCLUSIONS: IC-MPGN and C3G are rare disorders in children. Most patients have signs of complement activation associated with risk polymorphisms or likely pathogenic variants in complement-regulating genes. Steroids and mycophenolate mofetil seem to be effective and for some patients, eculizumab might be a treatment option. Outcome is heterogeneous and precise differentiation between IC-MPGN and C3G is still pending.