Effect of SGLT2 Inhibitor Dapagliflozin on Biomarkers of Tubular Injury in Patients with Acute Heart Failure: A Randomized Controlled Trial

Abstract

Abstract Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in acute heart failure (AHF) but are associated with a transient rise in serum creatinine. The aim of this study was to assess the effect of SGLT2 inhibitor on urinary biomarkers of tubular injury in patients with AHF. Patients who hospitalized for AHF were randomized to dapagliflozin added to standard of care or control group for 28 days. The primary outcome was the change of urinary [TIMP-2] x [IGFBP7] by NephroCheck® from baseline. Out of the 32 patients who underwent randomization, 25 eligible individuals were enrolled for analysis. Compared with control group, dapagliflozin group significantly reduced urinary [TIMP-2] x [IGFBP7] after 7 days [dapagliflozin: -0.03 ± 0.11 (ng/mL)2/1000; control: +0.4 ± 0.14 (ng/mL)2/1000; P = 0.022] and continue this trend until the end of the study. In terms of clinical outcomes, dapagliflozin has demonstrated a trend towards decrease in acute kidney injury (AKI) events compared to the control group (33.3% vs 46.2%; P = 0.513). The changes in serum creatinine, and adverse events showed no differences in either group. In conclusion, initiation of SGLT2 inhibitors in patients with AHF significantly decrease the urinary AKI risk markers TIMP-2 and IGFBP7, that supported protective effect of SGLT2 inhibitor on renal tubular injury. Trial registration number: The study was registered with the Thai Clinical Trials Registry TCTR20221003002.