Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease.

Adolescent Adrenal Cortex Hormones / therapeutic use Adult Child Complement C3 / analysis Disease Progression Drug Therapy, Combination Female Glomerulonephritis / diagnosis Humans Immunosuppressive Agents / adverse effects Male Middle Aged Mycophenolic Acid / adverse effects Recurrence Remission Induction Retrospective Studies Risk Factors Spain Time Factors Treatment Outcome Young Adult

Alternative complement pathway C3 glomerulopathy mycophenolate mofetil

Journal

Clinical journal of the American Society of Nephrology : CJASN

ISSN: 1555-905X

Titre abrégé: Clin J Am Soc Nephrol

Pays: United States

ID NLM: 101271570

Informations de publication

Date de publication:
07 09 2020

Historique:

received: 13 12 2019

accepted: 26 05 2020

pubmed: 21 8 2020

medline: 15 12 2021

entrez: 21 8 2020

Statut: ppublish

Résumé

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. 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 ( 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. The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.

Sections du résumé

BACKGROUND AND OBJECTIVES

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 (

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.

Identifiants

DOI: 10.2215/CJN.15241219 PMID: 32816888 PMC: PMC7480558

pubmed: 32816888

pii: 01277230-202009000-00013

doi: 10.2215/CJN.15241219

pmc: PMC7480558

doi:

Substances chimiques

Adrenal Cortex Hormones 0

C3 protein, human 0

Complement C3 0

Immunosuppressive Agents 0

Mycophenolic Acid HU9DX48N0T

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1287-1298

Commentaires et corrections

Type : CommentIn

Type : ErratumIn

Informations de copyright

Références

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