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. 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 have suggested that empagliflozin, a renal sodium-glucose cotransporter 2 (SGLT2) inhibitor, may assist in treatment of inflammatory diseases, our objective was to examine the effect of empagliflozin on acute sepsis-induced renal injury. Method: Mice were treated with empagliflozin or vehicle for 3 days prior to a single lipopolysaccharide (LPS) injection to induce sepsis. In another cohort, mice were injected with LPS for 3 hours to induce sepsis, then treated with empagliflozin. In both instances, mice were examined 24 hours after the injection of LPS. Findings: 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 our LPS-model. Interpretation: The findings of this study suggest that empagliflozin could be repurposed to reduce morbidity and mortality in patients with acute septic renal injury. Fund: This work was supported by a grant from CIHR to JRBD. Funding Statement: This work was supported by a grant from CIHR to JRBD. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All animal procedures were approved by the University of Alberta Institutional Animal Care and Use Committee, which conforms to the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health and the principles for biomedical research involving animals developed by the Council for International Organizations of Medical Sciences.