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 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 to 54.8%) and eGFR by 5.1 (2.0 to 8.1) ml/min/1.73m² compared to placebo. Compared to placebo, dapagliflozin did not change glomerular charge or size selectivity index. Dapagliflozin decreased urinary KIM‐1 excretion by 22.6% (0.3 to 39.8%; p=0.05) and IL‐6 excretion by 23.5% (1.4 to 40.6%; p=0.04) 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=0.05) and KIM‐1 (r=0.39, p=0.05). In conclusion, the albuminuria lowering effect of 6 weeks dapagliflozin therapy may be due to decreased intraglomerular pressure or reduced tubular cell injury.