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PLoS One. 2017 Oct 30;12(10):e0186910. doi: 10.1371/journal.pone.0186910. eCollection 2017.

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

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Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
Division of Endocrinology, University Health Network, University of Toronto, Toronto, Canada.
Department of Clinical Pharmacology University Medical Center Groningen, Groningen, the Netherlands.
Instituto de Investigación Sanitaria Fundación Jiménez Díaz. Fundación Renal Iñigo Álvarez de Toledo. Universidad Autónoma de Madrid. REDinREN, Madrid, Spain.
Mosaiques diagnostics GmbH, Hanover, Germany.
BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.


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.

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