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.

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