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C3 Glomerulopathy and Related Disorders in Children.

Lookup NU author(s): Professor Kevin MarchbankORCiD, Dr Isabel Pappworth, Harriet Denton, Kate Cooke, Grant Richardson, Dr Valerie Wilson, Professor Claire Harris, Professor Tim Goodship, Professor David KavanaghORCiD, Dr Sally Johnson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background and objectives: Membranoproliferative Glomerulonephritis (MPGN) and C3 Glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific aetiological data for paediatric MPGN/C3 glomerulopathy are lacking, and outcome data are based upon retrospective studies without aetiological data. Design, setting, participants, and measurements: Eighty prevalent pediatric patients with MPGN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using COX proportional hazards model. Kidney and transplant graft survival was determined using Kaplan-Meier method. Results: Central histology review determined 39 C3 glomerulopathy, 31 immune-complex MPGN and 10 immune-complex glomerulonephritis (GN) cases. Patients were aged 2-15 (median 9 (IQR 7-11) years. Median complement C3 and C4 levels were 0.31g/L and 0.14g/L respectively; acquired (anti-complement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% patients respectively, across all groups including immune-complex GN. Median follow-up was 5.18 (IQR 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure with 9 transplants performed in 8 patients, 2 of which failed due to recurrent disease. Presence of >50% crescents on initial biopsy was the sole variable associated with kidney failure in multivariable analysis (Hazard Ratio 6.2, p = 0.045; 95% CI 1.05 to 36.6). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on initial biopsy. Conclusions: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric MPGN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.34551983

Publication metadata

Author(s): Wong E, Marchbank K, Lomax-Browne H, Pappworth I, Denton H, Cooke K, Ward S, McLoughlin AC, Richardson G, Wilson V, Harris C, Morgan BP, Hakobyan S, McAlinden P, Gale D, Maxwell H, Christian M, Malcomson R, Goodship T, Marks S, Pickering M, Kavanagh D, Cook H, Johnson S

Publication type: Article

Publication status: Published

Journal: Clinical Journal of the American Society of Nephrology

Year: 2021

Volume: 16

Issue: 11

Pages: 1639-1651

Print publication date: 01/11/2021

Online publication date: 22/09/2021

Acceptance date: 17/09/2021

Date deposited: 16/10/2023

ISSN (print): 1555-9041

ISSN (electronic): 1555-905X

Publisher: American Society of Nephrology


DOI: 10.2215/CJN.00320121

PubMed id: 34551983


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Funder referenceFunder name
Kids Kidney Research
Medical Research Council
MR/K023519/1Medical Research Council (MRC)
Northern Counties Kidney Research Fund
St. Peter’s Trust for Kidney, Bladder and Prostate Research
Wellcome Trust