C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes.
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| Abstract | BACKGROUND AND OBJECTIVES: Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 80 prevalent pediatric patients with membranoproliferative GN/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 a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan-Meier method. RESULTS: Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2-15 (median, 9; interquartile range, 7-11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P<0.05). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on the initial biopsy specimen. CONCLUSIONS: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/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.
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| Authors | Edwin K S Wong, Kevin J Marchbank, Hannah Lomax-Browne, Isabel Y Pappworth, Harriet Denton, Katie Cooke, Sophie Ward, Amy-Claire McLoughlin, Grant Richardson, Valerie Wilson, Claire L Harris, B Paul Morgan, Svetlana Hakobyan, Paul McAlinden, Daniel P Gale, Heather Maxwell, Martin Christian, Roger Malcomson, Timothy H J Goodship, Stephen D Marks, Matthew C Pickering, David Kavanagh, H Terence Cook, Sally A Johnson, MPGN/DDD/C3 Glomerulopathy Rare Disease Group and National Study of MPGN/DDD/C3 Glomerulopathy Investigators |
| Journal | Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 16 Issue 11 Pg. 1639-1651 (11 2021) ISSN: 1555-905X [Electronic] United States |
| PMID | 34551983 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 by the American Society of Nephrology. |
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