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A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. Multicenter, retrospective cohort study. 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). Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. Time to kidney failure. Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) 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 (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (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. Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. 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. Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.


Fernando Caravaca-Fontán, Hernando Trujillo, Marina Alonso, Montserrat Díaz-Encarnación, Virginia Cabello, Gema Ariceta, Luis F Quintana, Helena Marco, Xoana Barros, Natalia Ramos, Nuria Rodríguez-Mendiola, Sonia Cruz, Gema Fernández-Juárez, Eva Rodríguez, Francisco de la Cerda, Ana Pérez de José, Inmaculada López, Loreto Fernández, Vanessa Pérez Gómez, Ana Ávila, Luis Bravo, Javier Lumbreras, Natalia Allende, Maria Dolores Sanchez de la Nieta, Teresa Olea, Marta Melgosa, Ana Huerta, Rosa Miquel, Carmen Mon, Gloria Fraga, Alberto de Lorenzo, Juliana Draibe, Fayna González, Amir Shabaka, Maria Luisa Illescas, Consuelo Calvo, Victoria Oviedo, Iara Da Silva, Elena Goicoechea de Jorge, Francisco Caravaca, Manuel Praga, C3G Study Group of the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Validation of a Histologic Scoring Index for C3 Glomerulopathy. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021 May;77(5):684-695.e1

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PMID: 33359150

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