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Membranoproliferative glomerulonephritis and C3 glomerulopathy in children: change in treatment modality? A report of a case series


Spartà, Giuseppina; Gaspert, Ariana; Neuhaus, Thomas J; Weitz, Marcus; Mohebbi, Nilufar; Odermatt, Urs; Zipfel, Peter F; Bergmann, Carsten; Laube, Guido F (2018). Membranoproliferative glomerulonephritis and C3 glomerulopathy in children: change in treatment modality? A report of a case series. Clinical Kidney Journal, 11(4):479-490.

Abstract

Background Membranoproliferative glomerulonephritis (MPGN) with immune complexes and C3 glomerulopathy (C3G) in children are rare and have a variable outcome, with some patients progressing to end-stage renal disease (ESRD). Mutations in genes encoding regulatory proteins of the alternative complement pathway and of complement C3 (C3) have been identified as concausative factors.
Methods Three children with MPGN type I, four with C3G, i.e. three with C3 glomerulonephritis (C3GN) and one with dense deposit disease (DDD), were followed. Clinical, autoimmune data, histological characteristics, estimated glomerular filtration rate (eGFR), proteinuria, serum C3, genetic and biochemical analysis were assessed.
Results The median age at onset was 7.3 years and the median eGFR was 72 mL/min/1.73 m. Six children had marked proteinuria. All were treated with renin-angiotensin-aldosterone system (RAAS) blockers. Three were given one or more immunosuppressive drugs and two eculizumab. At the last median follow-up of 9 years after diagnosis, three children had normal eGFR and no or mild proteinuria on RAAS blockers only. Among four patients without remission of proteinuria, genetic analysis revealed mutations in complement regulator proteins of the alternative pathway. None of the three patients with immunosuppressive treatment achieved partial or complete remission of proteinuria and two progressed to ESRD and renal transplantation. Two patients treated with eculizumab revealed relevant decreases in proteinuria.
Conclusions In children with MPGN type I and C3G, the outcomes of renal function and response to treatment modality show great variability independent from histological diagnosis at disease onset. In case of severe clinical presentation at disease onset, early genetic and biochemical analysis of the alternative pathway dysregulation is recommended. Treatment with eculizumab appears to be an option to slow disease progression in single cases.

Abstract

Background Membranoproliferative glomerulonephritis (MPGN) with immune complexes and C3 glomerulopathy (C3G) in children are rare and have a variable outcome, with some patients progressing to end-stage renal disease (ESRD). Mutations in genes encoding regulatory proteins of the alternative complement pathway and of complement C3 (C3) have been identified as concausative factors.
Methods Three children with MPGN type I, four with C3G, i.e. three with C3 glomerulonephritis (C3GN) and one with dense deposit disease (DDD), were followed. Clinical, autoimmune data, histological characteristics, estimated glomerular filtration rate (eGFR), proteinuria, serum C3, genetic and biochemical analysis were assessed.
Results The median age at onset was 7.3 years and the median eGFR was 72 mL/min/1.73 m. Six children had marked proteinuria. All were treated with renin-angiotensin-aldosterone system (RAAS) blockers. Three were given one or more immunosuppressive drugs and two eculizumab. At the last median follow-up of 9 years after diagnosis, three children had normal eGFR and no or mild proteinuria on RAAS blockers only. Among four patients without remission of proteinuria, genetic analysis revealed mutations in complement regulator proteins of the alternative pathway. None of the three patients with immunosuppressive treatment achieved partial or complete remission of proteinuria and two progressed to ESRD and renal transplantation. Two patients treated with eculizumab revealed relevant decreases in proteinuria.
Conclusions In children with MPGN type I and C3G, the outcomes of renal function and response to treatment modality show great variability independent from histological diagnosis at disease onset. In case of severe clinical presentation at disease onset, early genetic and biochemical analysis of the alternative pathway dysregulation is recommended. Treatment with eculizumab appears to be an option to slow disease progression in single cases.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:August 2018
Deposited On:04 Sep 2018 15:39
Last Modified:17 Sep 2019 19:26
Publisher:Oxford University Press
ISSN:2048-8505
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ckj/sfy006
PubMed ID:30094012

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