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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
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
URL: https://doi.org/10.2215/CJN.00320121
DOI: 10.2215/CJN.00320121
PubMed id: 34551983
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