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


ABSTRACT: 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.

SUBMITTER: Dekkers CCJ 

PROVIDER: S-EPMC6055757 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Dekkers Claire C J CCJ   Petrykiv Sergei S   Laverman Gozewijn D GD   Cherney David Z DZ   Gansevoort Ron T RT   Heerspink Hiddo J L HJL  

Diabetes, obesity & metabolism 20180423 8


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  ...[more]

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