Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease.
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| Abstract | BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure). RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse. CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.
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| Authors | Fernando Caravaca-Fontán, Montserrat M Díaz-Encarnación, Laura Lucientes, Teresa Cavero, Virginia Cabello, Gema Ariceta, Luis F Quintana, Helena Marco, Xoana Barros, Natalia Ramos, Nuria Rodríguez-Mendiola, Sonia Cruz, Gema Fernández-Juárez, Adela Rodríguez, Ana Pérez de José, Cristina Rabasco, Raquel Rodado, Loreto Fernández, Vanessa Pérez Gómez, Ana I Ávila, Luis Bravo, Javier Lumbreras, Natalia Allende, Maria Dolores Sanchez de la Nieta, Eva Rodríguez, Teresa Olea, Marta Melgosa, Ana Huerta, Rosa Miquel, Carmen Mon, Gloria Fraga, Alberto de Lorenzo, Juliana Draibe, Marta Cano-Megías, Fayna González, Amir Shabaka, Maria Esperanza López-Rubio, María Ángeles Fenollosa, Luis Martín-Penagos, Iara Da Silva, Juana Alonso Titos, Santiago Rodríguez de Córdoba, Elena Goicoechea de Jorge, Manuel Praga, Spanish Group for the Study of Glomerular Diseases GLOSEN |
| Journal | Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 15 Issue 9 Pg. 1287-1298 (09 07 2020) ISSN: 1555-905X [Electronic] United States |
| PMID | 32816888 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2020 by the American Society of Nephrology. |
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