C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Wong, Edwin K.S.; Marchbank, Kevin J.; Lomax-Browne, Hannah; Pappworth, Isabel Y.; Denton, Harriet; Cooke, Katie; Ward, Sophie; McLoughlin, Amy-Claire; Richardson, Grant; Wilson, Valerie; Harris, Claire L.; Morgan, B. Paul; Hakobyan, Svetlana; McAlinden, Paul; Gale, Daniel P.; Maxwell, Heather; Christian, Martin; Malcomson, Roger; Goodship, Timothy H.J.; Marks, Stephen D.; Pickering, Matthew C.; Kavanagh, David; Cook, H. Terence; Johnson, Sally A.
• Other Names: Brimble Su author non-byline.; Cook H. Terence author non-byline.; Gale Daniel P. author non-byline.; Gibbs Julie author non-byline.; Gilbert Rodney author non-byline.; Harper Lorraine author non-byline.; Harris Claire L. author non-byline.; Jessup Kim author non-byline.; Johnson Sally A. author non-byline.; Jones Helen author non-byline.; Kavanagh David author non-byline.; Levine Adam author non-byline.; Lomax-Browne Hannah author non-byline.; Longfellow Andrew author non-byline.; Malcomson Roger author non-byline.; Marchbank Kevin J. author non-byline.; Marks Stephen D. author non-byline.; Maxwell Heather author non-byline.; McAlinden Paul author non-byline.; Milford David author non-byline.; Pickering Matthew C. author non-byline.; Richardson Sandra author non-byline.; Richardson Stephen author non-byline.; Sebire Neil author non-byline.; Taylor Mark author non-byline.; Wessels Julie author non-byline.; Whittall Sarah author non-byline.; Wong Edwin K.S. author non-byline.; Christian Martin author non-byline.; Finlay Eric author non-byline.; Gilbert Rodney author non-byline.; Hegde Shivaram author non-byline.; Johnson Sally A. author non-byline.; Jones Caroline author non-byline.; Marks Stephen D. author non-byline.; Maxwell Heather author non-byline.; Milford David author non-byline.; Saleem Moin author non-byline.; Sinha Manish author non-byline.; Webb Nick author non-byline.;
• Is Part Of: Clinical journal of the American Society of Nephrology. Volume 16:Issue 11(2021)
• Page Start: 1639
• Page End: 1651
• Publication Date: 2021-11
• Subjects: complement -- membranoproliferative glomerulonephritis (MPGN) -- children -- C3 glomerulopathy
• DOI: 10.2215/CJN.00320121
• Languages: English
• ISSNs: 1555-9041

Abstract

Visual Abstract: 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.