Investigation of the effects of empagliflozin on acute kidney damage in lipopolysaccharide induced sepsis in rats

Sepsis is a fatal disease that progresses with uncontrolled inflammation and acute septic renal injury and kidney failure are frequently observed in sepsis. Mortality is significantly higher in sepsis patients who developed acute kidney injury. The SGLT-2 protein is common in the convoluted portion of the renal proximal tubules, and approximately 90% of the reabsorption of glucose filtered from the glomeruli is via SGLT-2. SGLT-2 inhibitors inhibit the reabsorption of glucose from the tubules and are used in the treatment of type 2 diabetes. Empagliflozin is an SGLT-2 inhibitor used in the treatment of type 2 diabetes and heart failure, and the effects of this widely used drug on other diseases are a popular research topic. Studies have shown that empagliflozin may have an antiinflammatory effect and have direct protective effects on the kidney. In this study, the effect of empagliflozin treatment on physiologic and renal functions in LPS-induced acute septic renal injury model was evaluated. Empagliflozin increased urinary glucose excretion and decreased the urinary leukocyte amount whose excretion increased in sepsis. Empagliflozin treatment did not reverse the decreased vascular blood flow in kidney, liver, and ileum associated with sepsis. Ureteral urine outflow was decreased in acute septic renal injury and empagliflozin treatment did not have a corrective effect. In renal artery branches, phenylephrine responses decreased in sepsis, and empagliflozin treatment had a corrective effect. Angiotensin-II contractile responses increased in sepsis in the second branch of the renal artery, and empagliflozin treatment corrected this decrease. In renal artery branches acetylcholine responses were decreased in sepsis and empagliflozin had a corrective effect in the second branch of the renal arter. SNP responses in renal artery branches did not change in sepsis. Contractile responses seen with electrical field stimulation were decreased in renal artery branches in sepsis, but empagliflozin did not have a corrective effect. Empagliflozin treatment had a corrective effect on the histopathological damage seen in the liver and ileum in sepsis, but not in the kidney.