Empagliflozin suppresses inflammation and protects against acute septic renal injury

Abstract

Background: Sepsis-induced systemic inflammation response syndrome is the leading cause of morbidity and mortality among patients in intensive care units in North America. While sepsis is associated with multiple organ damage, acute renal injury represents a hallmark of sepsis. Since systemic and renal inflammation is known to play a vital role in morbidity and mortality associated with sepsis, identifying a potent anti-inflammatory agent may help minimize morbidity and mortality associated with acute septic kidney injury. Since recent work has suggested that empagliflozin, a renal sodium-glucose cotransporter 2 (SGLT2) inhibitor, may assist in the treatment of inflammatory diseases, our objective was to examine the effect of empagliflozin on acute sepsis-induced renal injury.

Method: Mice were treated with three daily doses of empagliflozin or vehicle, with lipopolysaccharide (LPS) administered on the third day, at the same time as the third dose of empagliflozin or vehicle. In another cohort, mice were injected with a single dose of LPS 3 h before a dose of empagliflozin.

Results: Our results show that empagliflozin improves survival in a mouse model of LPS-induced septic shock. We further demonstrate that the beneficial effects of empagliflozin are likely mediated via reducing LPS-induced acute renal injury. Moreover, our data indicate that empagliflozin significantly reduces systemic and renal inflammation to contribute to the improvements observed in an LPS-model of acute septic renal injury.

Conclusion: Overall, the findings of this study suggest that empagliflozin could be repurposed to reduce morbidity and mortality in patients with acute septic renal injury.

Trial registration: Not applicable.

Keywords: Empagliflozin; Inflammation; Renal injury; Sepsis.