The effect of sodium/glucose cotransporter 2 (SGLT2) inhibition on the urinary proteome

Cherney, D., Perkins, B. A., Lytvyn, Y., Heerspink, H., Rodríguez-Ortiz, M. E. and Mischak, H. (2017) The effect of sodium/glucose cotransporter 2 (SGLT2) inhibition on the urinary proteome. PLoS ONE, 12(10), e0186910. (doi: 10.1371/journal.pone.0186910) (PMID:29084249) (PMCID:PMC5662219)

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Abstract

Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides. We further assessed the association of these changes with CKD in an independent cohort, and with a previously established urinary proteomic panel, termed CKD273. 107 individual peptides significantly changed after treatment. The majority of the empagliflozin-induced changes were in the direction of “CKD absent” when compare to patients with CKD and controls. A classifier consisting of these 107 peptides scored significantly different in controls, in comparison to CKD patients. However, empagliflozin did not impact the CKD273 classifier. Our data indicate that empagliflozin induces multiple significant changes in the urinary proteomic markers such as mucin and clusterin. The relationship between empagliflozin-induced proteomic changes and clinical outcomes merits further investigation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Authors: Cherney, D., Perkins, B. A., Lytvyn, Y., Heerspink, H., Rodríguez-Ortiz, M. E., and Mischak, H.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Cherney et al.
First Published:First published in PLoS ONE 12(10): e0186910
Publisher Policy:Reproduced under a Creative Commons License

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