Natural History of C3 Glomerulopathy and Immune Complex-Associated Membranoproliferative Glomerulonephritis in Children

Background: – C3 glomerulopathy (C3G) and immune complex-associated membranoproliferative glomerulonephritis (IC-MPGN) are rare complement-mediated kidney diseases with a high risk of progression to kidney failure. Little is known about the natural history of these diseases in children, limiting our understanding of risk factors for progressive kidney disease. Methods: – Using a computable phenotype algorithm, a pediatric cohort with C3G or IC-MPGN was identified at seven institutions in PEDSnet, a national network of pediatric health systems which aggregate electronic health record data and collaborate on pragmatic research studies. Discrete data elements were captured from electronic health records and additional clinical and histopathologic data were extracted by standardized chart review by pediatric nephrologists. Biopsy diagnosis was classified as C3G or IC-MPGN by applying an algorithm based on immunofluorescence and electron microscopy and supplemented with manual chart review. Kaplan-Meier survival curves were utilized to compare the risk of reaching a composite kidney outcome of 50% reduction in estimated glomerular filtration rate (eGFR), initiation of maintenance dialysis, or kidney transplantation. Results: – Of 204 patients with MPGN identified by the computable phenotype algorithm and chart review, 159 could be further classified as C3G or IC-MPGN based on available biopsy data. There were no significant differences in baseline serum albumin, C3 level, urine protein/creatinine ratio, or eGFR between C3G or IC-MPGN. Patients with C3G and IC-MPGN had similar rates of progression to the composite kidney outcome, and a low serum C3 level at baseline was associated with this composite outcome. Conclusion: – Using large-scale, real-world multi-institutional data, we investigated the natural history of a large contemporary cohort of children with MPGN. As patients classified as having C3G compared to IC-MPGN had similar baseline clinical characteristics and rates of progressive disease despite untargeted treatment approaches, the availability of newer complement-targeted agents hold the promise of benefit to this population.