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

KEY POINTS: C3 glomerulopathy and immune complex-associated membranoproliferative glomerulonephritis in children have similar degrees of proteinuria, hypoalbuminemia, hypertension, and hypocomplementemia at diagnosis. C3 glomerulopathy and immune complex-associated membranoproliferative glomerulonephritis in children progress similarly to a composite outcome of CKD, dialysis, or kidney transplantation. A low level of C3 at baseline is associated with achieving the composite outcome.

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 on the basis of immunofluorescence and electron microscopy and supplemented with manual chart review. Kaplan-Meier survival curves were used to compare the risk of reaching a composite kidney outcome of 50% reduction in eGFR, initiation of maintenance dialysis, or kidney transplantation.

RESULTS

Of 204 patients with membranoproliferative glomerulonephritis identified by the computable phenotype algorithm and chart review, 159 could be further classified as C3G or IC-MPGN on the basis of available biopsy data. There were no significant differences in baseline serum albumin, C3 level, urine protein/creatinine ratio, or eGFR between C3G and 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 membranoproliferative glomerulonephritis. Because patients classified as having C3G compared with 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.