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Observational Study
. 2020 Sep 7;15(9):1287-1298.
doi: 10.2215/CJN.15241219. Epub 2020 Aug 19.

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease

Fernando Caravaca-Fontán  1   2 , Montserrat M Díaz-Encarnación  3 , Laura Lucientes  4 , Teresa Cavero  5 , Virginia Cabello  6 , Gema Ariceta  7 , Luis F Quintana  8 , Helena Marco  9 , Xoana Barros  10 , Natalia Ramos  11 , Nuria Rodríguez-Mendiola  12 , Sonia Cruz  13 , Gema Fernández-Juárez  14 , Adela Rodríguez  15 , Ana Pérez de José  16 , Cristina Rabasco  17 , Raquel Rodado  18 , Loreto Fernández  19 , Vanessa Pérez Gómez  20 , Ana I Ávila  21 , Luis Bravo  22 , Javier Lumbreras  23 , Natalia Allende  24 , Maria Dolores Sanchez de la Nieta  25 , Eva Rodríguez  26 , Teresa Olea  27 , Marta Melgosa  28 , Ana Huerta  29 , Rosa Miquel  30 , Carmen Mon  31 , Gloria Fraga  32 , Alberto de Lorenzo  33 , Juliana Draibe  34 , Marta Cano-Megías  35 , Fayna González  36 , Amir Shabaka  37 , Maria Esperanza López-Rubio  38 , María Ángeles Fenollosa  39 , Luis Martín-Penagos  40 , Iara Da Silva  3 , Juana Alonso Titos  41 , Santiago Rodríguez de Córdoba  42 , Elena Goicoechea de Jorge  3   42 , Manuel Praga  1   2 ; Spanish Group for the Study of Glomerular Diseases GLOSEN
Affiliations
Observational Study

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease

Fernando Caravaca-Fontán et al. Clin J Am Soc Nephrol. .

Erratum in

  • Correction.
    [No authors listed] [No authors listed] Clin J Am Soc Nephrol. 2020 Dec 7;15(12):1817. doi: 10.2215/CJN.16691020. Epub 2020 Nov 9. Clin J Am Soc Nephrol. 2020. PMID: 33168634 Free PMC article. No abstract available.

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.

Keywords: Alternative complement pathway; C3 glomerulopathy; mycophenolate mofetil.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart of patients included in the study.
Figure 2.
Figure 2.
Kaplan–Meier curves for kidney survival according to therapeutic regimens. The time point 0 represents the onset of treatment. MMF, mycophenolate mofetil.
Figure 3.
Figure 3.
Kaplan–Meier curves for kidney survival according to treatment with mycophenolate mofetil plus corticosteroids versus other immunosuppression in the propensity matched cohort.
Figure 4.
Figure 4.
Kidney survival in patients treated with corticosteroids plus mycophenolate mofetil versus other regimens according to the presence of pathogenic variants or autoantibodies.
See this image and copyright information in PMC

Comment in

References

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