Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease
Por:
Caravaca-Fontán F, Díaz-Encarnación MM, Lucientes L, Cavero T, Cabello V, Ariceta G, Quintana LF, Marco H, Barros X, Ramos N, Rodríguez-Mendiola N, Cruz S, Fernández-Juárez G, Rodríguez A, Pérez de José A, Rabasco C, Rodado R, Fernández L, Pérez Gómez V, Ávila AI, Bravo L, Lumbreras J, Allende N, Sanchez de la Nieta MD, Rodríguez E, Olea T, Melgosa M, Huerta A, Miquel R, Mon C, Fraga G, de Lorenzo A, Draibe J, Cano-Megías M, González F, Shabaka A, López-Rubio ME, Fenollosa MÁ, Martín-Penagos L, Da Silva I, Alonso Titos J, Rodríguez de Córdoba S, Goicoechea de Jorge E and Praga M
Publicada:
7 sep 2020
Ahead of Print:
19 ago 2020
Resumen:
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.
Filiaciones:
Caravaca-Fontán F:
Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain
Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
Díaz-Encarnación MM:
Department of Nephrology, Fundación Puigvert, Barcelona, Spain
Lucientes L:
Department of Immunology, Universidad Complutense de Madrid, Madrid, Spain
Cavero T:
Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
Cabello V:
Department of Nephrology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Ariceta G:
Department of Pediatric Nephrology, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain
Quintana LF:
Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Universitat de Barcelona,Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR)
Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain
Marco H:
Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
Barros X:
Department of Nephrology, Hospital Universitario Doctor Josep Trueta, Gerona, Spain
Ramos N:
Department of Nephrology, Hospital Universitario Vall d'Hebron, Barcelona, Spain
Rodríguez-Mendiola N:
Department of Nephrology, Hospital Universitario Ramón y Cajal, Madrid, Spain
Cruz S:
Department of Nephrology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain
Fernández-Juárez G:
Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
Rodríguez A:
Department of Pediatric Nephrology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Pérez de José A:
Department of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain
Rabasco C:
Department of Nephrology, Hospital Universitario Reina Sofía, Córdoba, Spain
Rodado R:
Department of Nephrology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
Fernández L:
Department of Nephrology, Complejo Hospitalario de Navarra, Navarra, Spain
Pérez Gómez V:
Department of Nephrology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
:
Department of Nephrology, Hospital Universitario Doctor Peset, Valencia, Spain
Bravo L:
Department of Nephrology, Hospital Universitario A Coruña, La Coruña, Spain
Lumbreras J:
Pediatric Nephrology Unit, Hospital Universitario Son Espases, Balearic Islands Health Research Institute, Palma de Mallorca, Spain
Allende N:
Department of Nephrology, Hospital Universitario Son Espases, Palma de Mallorca, Spain
Sanchez de la Nieta MD:
Department of Nephrology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
Rodríguez E:
Department of Nephrology, Hospital del Mar, Barcelona, Spain
Olea T:
Department of Nephrology, Hospital Universitario La Paz, Madrid, Spain
Melgosa M:
Department of Pediatric Nephrology, Hospital Universitario La Paz, Madrid, Spain
Huerta A:
Department of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, Spain
Miquel R:
Department of Nephrology, Hospital Universitario Canarias, Tenerife, Spain
Mon C:
Department of Nephrology, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain
Fraga G:
Department of Pediatric Nephrology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
de Lorenzo A:
Department of Nephrology, Hospital Universitario de Getafe, Madrid, Spain
Draibe J:
Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain
Cano-Megías M:
Department of Nephrology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
González F:
Department of Nephrology, Hospital Doctor Negrín, Gran Canaria, Spain
Shabaka A:
Department of Nephrology, Hospital Universitario Clínico San Carlos, Madrid, Spain
López-Rubio ME:
Department of Nephrology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
:
Department of Nephrology, Hospital General Universitario de Castellón, Castellón, Spain
Martín-Penagos L:
Department of Nephrology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
Da Silva I:
Department of Nephrology, Fundación Puigvert, Barcelona, Spain
Alonso Titos J:
Department of Nephrology, Hospital Regional Universitario Carlos Haya, Málaga, Spain
Rodríguez de Córdoba S:
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid and Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain
Goicoechea de Jorge E:
Department of Nephrology, Fundación Puigvert, Barcelona, Spain
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid and Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain
Praga M:
Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
Green Published, Bronze
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