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

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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.

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Authors and Affiliations

  1. Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Johannes Holle

  2. Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Lena Berenberg-Goßler, Dominik Müller & Julia Thumfart

  3. Department of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Kaiyin Wu

  4. Department of Pediatrics and Adolescent Medicine, Pediatric Nephrology, Ulm University Medical Center, Ulm, Germany

    Ortraud Beringer & Florian Kropp

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  1. Johannes Holle
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Correspondence to Johannes Holle.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.

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Holle, J., Berenberg-Goßler, L., Wu, K. et al. Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in children and adolescents. Pediatr Nephrol 33, 2289–2298 (2018). https://doi.org/10.1007/s00467-018-4034-z

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  • DOI: https://doi.org/10.1007/s00467-018-4034-z

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