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Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool.

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journal contribution
posted on 10.06.2020, 10:48 by Sean J Barbour, Mark Canney, Rosanna Coppo, Hong Zhang, Zhi-Hong Liu, Yusuke Suzuki, Keiichi Matsuzaki, Ritsuko Katafuchi, Dilshani Induruwage, Lee Er, Heather N Reich, John Feehally, Jonathan Barratt, Daniel C Cattran, International IgA Nephropathy Network
Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria οϕ 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

Funding

Dr. Barbour is a Scholar with the Michael Smith Foundation for Health Research. Funding support for this project was provided by grant funding from the Canadian Institutes of Health Research (PCG-155557). The VALIGA study 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 (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.

History

Citation

Kidney International Available online 25 May 2020 In Press, Journal Pre-proof

Version

AM (Accepted Manuscript)

Published in

Kidney international

Publisher

Elsevier BV

issn

0085-2538

eissn

1523-1755

Acceptance date

02/04/2020

Copyright date

2020

Language

eng

Publisher version

https://www.sciencedirect.com/science/article/pii/S0085253820305445