C3 Glomerulopathy and related disorders in children

Wong, Edwin, Marchbank, Kevin, Lomax-Browne, Hannah, Pappworth, Isabel, Denton, Harriet, Cooke, Katie, Ward, Sophie, McLoughlin, Amy-Claire, Richardson, Grant, Wilson, Valerie, Harris, Claire, Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676, Hakobyan, Svetlana, McAlinden, Paul, Gale, Daniel, Maxwell, Heather, Christian, Martin, Malcomson, Roger, Goodship, Timothy, Marks, Stephen, Pickering, Matthew, Kavanagh, David, Cook, H. Terence and Johnson, Sally 2021. C3 Glomerulopathy and related disorders in children. Clinical Journal of the American Society of Nephrology 16 (11) , pp. 1639-1651. 10.2215/CJN.00320121

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Society of Nephrology
ISSN:	1555-9041
Date of First Compliant Deposit:	7 October 2021
Date of Acceptance:	17 September 2021
Last Modified:	07 Nov 2023 08:00
URI:	https://orca.cardiff.ac.uk/id/eprint/144739

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