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C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes

Title: C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes
Authors: Wong, EKS; Marchbank, KJ; Lomax-Browne, H; Pappworth, IY; Denton, H; Cooke, K; Ward, S; McLoughlin, A-C; Richardson, G; Wilson, V; Harris, CL; Morgan, BP; Hakobyan, S; McAlinden, P; Gale, DP; Maxwell, H; Christian, M; Malcomson, R; Goodship, THJ; Marks, SD; Pickering, MC; Kavanagh, D; Cook, HT; Johnson, SA; MPGN/DDD/C3 Glomerulopathy Rare Disease Group and National Study
Source: Clinical Journal of the American Society of Nephrology (CJASN) , 16 (11) pp. 1639-1651. (2021)
Publication Year: 2021
Collection: University College London: UCL Discovery
Subject Terms: C3 glomerulopathy; children; complement; membranoproliferative glomerulonephritis (MPGN)
Description: 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; P50% 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 ...
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10139221/1/2021%20Wong%20MPGN%20and%20C3G%20in%20children%20CJASN%202021_submitted.pdf; https://discovery.ucl.ac.uk/id/eprint/10139221/
Availability: https://discovery.ucl.ac.uk/id/eprint/10139221/1/2021%20Wong%20MPGN%20and%20C3G%20in%20children%20CJASN%202021_submitted.pdf; https://discovery.ucl.ac.uk/id/eprint/10139221/
Rights: open
Accession Number: edsbas.E99CD72E
Database: BASE