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Diabetes Obes Metab. 2018 Aug;20(8):1988-1993. doi: 10.1111/dom.13301. Epub 2018 Apr 23.

Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers.

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Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Nephrology, Ziekenhuisgroep Twente, Almelo and Hengelo, The Netherlands.
Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Canada.
Department of Physiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada.


The mechanisms by which SGLT-2 inhibitors lower albuminuria are incompletely understood. We assessed in a post-hoc analysis of a cross-over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM-1, NGAL and LFABP) and inflammatory markers (urinary MCP-1 and IL-6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%-54.8%) and eGFR by 5.1 (2.0-8.1) mL/min/1.73m2 compared to placebo. Dapagliflozin did not change glomerular charge or size selectivity index compared to placebo. Dapagliflozin decreased urinary KIM-1 excretion by 22.6% (0.3%-39.8%; P = .05) and IL-6 excretion by 23.5% (1.4%-40.6%; P = .04) compared to placebo, whereas no changes in NGAL, LFABP and MCP-1 were observed. During dapagliflozin treatment, changes in albuminuria correlated with changes in eGFR (r = 0.36; P = .05) and KIM-1 (r = 0.39; P = .05). In conclusion, the albuminuria-lowering effect of 6 weeks of dapagliflozin therapy may be the result of decreased intraglomerular pressure or reduced tubular cell injury.


KIM-1; MCP-1; SGLT-2; acute kidney injury; dapagliflozin; type 2 diabetes

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