Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease
Por:
Caravaca-Fontan, F, Diaz-Encarnacion, MM, Lucientes, L, Cavero, T, Cabello, V, Ariceta, G, Quintana, LF, Marco, H, Barros, X, Ramos, N, Rodriguez-Mendiola, N, Cruz, S, Fernandez-Juarez, G, Rodriguez, A, de Jose, AP, Rabasco, C, Rodado, R, Fernandez, L, Gomez, VP, Avila, AI, Bravo, L, Lumbreras, J, Allende, N, de la Nieta, MDS, Rodriguez, E, Olea, T, Melgosa, M, Huerta, A, Miquel, R, Mon, C, Fraga, G, de Lorenzo, A, Draibe, J, Cano-Megias, M, Gonzalez, F, Shabaka, A, Lopez-Rubio, ME, Fenollosa, MA, Martin-Penagos, L, Da Silva, I, Titos, JA, de Cordoba, SR, de Jorge, EG, Praga, M
Publicada:
7 sep 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-Fontan, F:
Inst Invest Hosp 12 Octubre, Madrid, Spain
Univ Complutense Madrid, Dept Med, Madrid, Spain
Diaz-Encarnacion, MM:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Lucientes, L:
Univ Complutense Madrid, Dept Immunol, Madrid, Spain
Cavero, T:
Hosp Univ 12 Octubre, Dept Nephrol, Madrid, Spain
Cabello, V:
Hosp Univ Virgen Rocio, Dept Nephrol, Seville, Spain
Ariceta, G:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Dept Pediat Nephrol, Barcelona, Spain
Quintana, LF:
Univ Barcelona, Dept Nephrol & Renal Transplantat, Hosp Clin Barcelona, Ctr Referencia Enfermedad Glomerular Compleja Sis, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
Marco, H:
Hosp Badalona Germans Trias & Pujol, Dept Nephrol, Barcelona, Spain
Barros, X:
Hosp Univ Doctor Josep Trueta, Dept Nephrol, Girona, Spain
Ramos, N:
Hosp Univ Vall dHebron, Dept Nephrol, Barcelona, Spain
Rodriguez-Mendiola, N:
Hosp Univ Ramon & Cajal, Dept Nephrol, Madrid, Spain
Cruz, S:
Hosp Univ Juan Ramon Jimenez, Dept Nephrol, Huelva, Spain
Fernandez-Juarez, G:
Hosp Univ Fdn Alcorcon, Dept Nephrol, Madrid, Spain
Rodriguez, A:
Hosp Univ Virgen Rocio, Dept Pediat Nephrol, Seville, Spain
de Jose, AP:
Hosp Univ Gregorio Maranon, Dept Nephrol, Madrid, Spain
Rabasco, C:
Hosp Univ Reina Sofia, Dept Nephrol, Cordoba, Spain
Rodado, R:
Hosp Univ Virgen Arrixaca, Dept Nephrol, Murcia, Spain
Fernandez, L:
Complejo Hosp Navarra, Dept Nephrol, Navarra, Spain
Gomez, VP:
Hosp Univ Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain
Avila, AI:
Hosp Univ Doctor Peset, Dept Nephrol, Valencia, Spain
Bravo, L:
Hosp Univ La Coruna, Dept Nephrol, La Coruna, Spain
Lumbreras, J:
Hosp Univ Son Espases, Balear Islands Hlth Res Inst, Pediat Nephrol Unit, Palma De Mallorca, Spain
Allende, N:
Hosp Univ Son Espases, Dept Nephrol, Palma De Mallorca, Spain
de la Nieta, MDS:
Hosp Gen Univ Ciudad Real, Dept Nephrol, Ciudad Real, Spain
Rodriguez, E:
Hosp Mar, Dept Nephrol, Barcelona, Spain
Olea, T:
Hosp Univ La Paz, Dept Nephrol, Madrid, Spain
Melgosa, M:
Hosp Univ La Paz, Dept Pediat Nephrol, Madrid, Spain
Huerta, A:
Hosp Univ Puerta Hierro, Dept Nephrol, Madrid, Spain
Miquel, R:
Hosp Univ Canarias, Dept Nephrol, Tenerife, Spain
Mon, C:
Hosp Univ Severo Ochoa, Dept Nephrol, Madrid, Spain
Fraga, G:
Univ Autonoma Barcelona, Hosp Santa Creu Sant Pau, Dept Pediat Nephrol, Barcelona, Spain
de Lorenzo, A:
Hosp Univ Getafe, Dept Nephrol, Madrid, Spain
Draibe, J:
Hosp Univ Bellvitge, Dept Nephrol, Barcelona, Spain
Cano-Megias, M:
Hosp Univ Asturias, Dept Nephrol, Madrid, Spain
Gonzalez, F:
Hosp Doctor Negrin, Dept Nephrol, Gran Canaria, Spain
Shabaka, A:
Hosp Univ Clin San Carlos, Dept Nephrol, Madrid, Spain
Lopez-Rubio, ME:
Complejo Hosp Univ Albacete, Dept Nephrol, Albacete, Spain
Fenollosa, MA:
Complejo Hosp Univ Albacete, Dept Nephrol, Albacete, Spain
Hosp Gen Univ Castellon, Dept Nephrol, Castellon de La Plana, Spain
Martin-Penagos, L:
Hosp Univ Marques Valdecilla, Dept Nephrol, Santander, Spain
Da Silva, I:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Titos, JA:
Hosp Reg Univ Carlos Haya, Dept Nephrol, Malaga, Spain
de Cordoba, SR:
CSIC, Ctr Invest Biol, Madrid, Spain
de Jorge, EG:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain
Praga, M:
Inst Invest Hosp 12 Octubre, Madrid, Spain
Univ Complutense Madrid, Dept Med, Madrid, Spain
Green Published
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