C3 Glomerulopathy (C3G) and Immune Complex-associated Membranoproliferative Glomerulonephritis (IC-MPGN) are diseases with distinct underlying pathophysiologic mechanisms. C3G is widely recognized to be due to defective regulation of the alternative complement pathway, whereas IC-MPGN is associated with classical complement pathway activation by circulating or in situ immune complex formation. Historically, however, these diseases were categorized as various subtypes of MPGN by their histological appearance by electron microscopy, which led to uncertainty as to the precise nature of their disease biology, as well as optimal treatment strategies. The literature describing the clinical characteristics, treatment response, and outcomes of patients with C3G and IC-MPGN are largely based on small retrospective studies, and primarily in adults. Extraction and rigorous phenotyping of C3G and IC-MPGN patients from a large multi-institutional data resource offers the opportunity to more fully characterize the natural history of C3G and IC-MPGN in children, as well as identify predictors of disease response to therapeutic interventions (both complement-targeted and immunosuppressive therapies).
Purpose, Goal, and Hypothesis:
The purpose of this study is to identify and conduct phenotypic characterization of children with C3G and IC-MPGN in PEDSnet using data science and chart review methods. The long-term goal of this work is to perform a large multi-institutional natural history study, compare clinical outcomes in C3G and IC-MPGN, and identify predictors of disease response or progression. We hypothesize that among pediatric patients with C3G and IC- will be identifiable subset(s) of patients who have optimal response to immunosuppression regimens and/or complement-targeted therapies. Patient sub-sets will be characterized by and histological, immunological, and clinical characteristics.