Validation of a Histologic Scoring Index for C3 Glomerulopathy

ABSTRACT Rationale Objective A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy proposed a prognostic Histologic Index (C3G-HI) that has not yet been validated. Our objective was to validate performance of the C3G-HI in a new patient population. Study Design Multicenter, retrospective cohort study. Setting Participants 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Predictors Demographic, clinical parameters, the C3G-HI Total Activity Score and the C3G-HI Total Chronicity Score. Outcome Time to kidney failure. Analytical Approach Intraclass correlation coefficients and the kappa statistic were used to summarize inter-rater reproducibility for assessment of histopathology on kidney biopsies. The nonlinear relationships of risk of kidney failure with the Total Activity Score and the Total Chronicity Score were modeled using Cox proportional hazards analysis that incorporated cubic splines. Results The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall mean age of 35±22 years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the Total Activity Score (ICC=0.63), and excellent for Total Chronicity Score (ICC=0.89). Baseline eGFR, 24-hour proteinuria and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables., Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the Total Activity Score and Total Chronicity Score were added to the model, only the latter was identified as an independent predictor of kidney failure. Limitations Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. Conclusions We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.