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C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes.
- Source :
-
Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2021 Nov; Vol. 16 (11), pp. 1639-1651. Date of Electronic Publication: 2021 Sep 22. - Publication Year :
- 2021
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2021 by the American Society of Nephrology.)
- Subjects :
- Adolescent
Child
Child, Preschool
Complement C3 genetics
Complement C3b immunology
Complement C4 metabolism
Complement Factor B immunology
Complement Factor H immunology
Disease Progression
Female
Follow-Up Studies
Glomerular Filtration Rate
Glomerulonephritis, Membranoproliferative pathology
Glomerulonephritis, Membranoproliferative therapy
Graft Survival
Humans
Kaplan-Meier Estimate
Kidney Failure, Chronic etiology
Kidney Failure, Chronic surgery
Kidney Transplantation
Male
Prognosis
Proportional Hazards Models
Prospective Studies
Recurrence
Registries
Risk Factors
Autoantibodies blood
Complement C3 metabolism
Glomerulonephritis, Membranoproliferative blood
Glomerulonephritis, Membranoproliferative etiology
Phenotype
Subjects
Details
- Language :
- English
- ISSN :
- 1555-905X
- Volume :
- 16
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Clinical journal of the American Society of Nephrology : CJASN
- Publication Type :
- Academic Journal
- Accession number :
- 34551983
- Full Text :
- https://doi.org/10.2215/CJN.00320121