Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy

International IgA Nephropathy Network, Mark Canney, Sean J. Barbour*, Yuyan Zheng, Rosanna Coppo, Hong Zhang, Zhi Hong Liu, Keiichi Matsuzaki, Yusuke Suzuki, Ritsuko Katafuchi, Heather N. Reich, Daniel Cattran, M. L. Russo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Background On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. Methods In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a $25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to,1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). Results During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. Conclusions Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.

Original languageEnglish
JournalJournal of the American Society of Nephrology
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2021

Bibliographical note

Funding Information:
D. Cattran reports receiving grants from Genentech and personal fees from Calliditis Pharmaceutical, Chemocentryx, Dimerix, Novartis, and Principia Biopharma, outside the submitted work. H. Reich reports having consultancy agreements with Calliditas, Omeros - Academic; receiving research funding from clinical trial recruitment from Alnylam, Calliditas, Chemocentryx, and Omeros; receiving Honoraria from Novartis; being a member of the Editorial Board of Kidney International and a scientific advisor to Omeros; other interests/relationships from peer-reviewed funding from the Kidney Foundation of Canada, Canadian Institutes for Health Research, Fast Foundation, and the Pearson Foundation. S. Barbour is a Scholar with the Michael Smith Foundation for Health Research. All remaining authors have nothing to disclose.

Funding Information:
Funding support for this project was provided by grant funding from the Canadian Institutes of Health Research (Institute of Nutrition, Metabolism and Diabetes, grant PCG-155557). The European Validation Study of the Oxford Classification of IgA Nephropathy (VALIGA) was supported by a grant from the first research call and the Immunonephrology Working Group of the European Renal Association—European Dialysis and Transplant Association. The Oxford derivation and North American Validation studies were supported by the International IgA Nephropathy Network, the Toronto GN Registry, and the Toronto General Hospital Foundation (Sorenson and McCann Fund). The funders had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.

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