Effects of glucagon-like peptide-1 on systemic hemodynamics, kidney function, and intrarenal oxygenation in sheep with sepsis-associated acute kidney injury

Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce chronic kidney disease progression in people with type 2 diabetes mellitus. Sepsis is the leading cause of acute kidney injury (AKI). This study investigated whether GLP-1 is renoprotective in an ovine model of gram-negative septic AKI. Methods Sixteen healthy merino ewes were surgically instrumented to measure mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion and oxygenation, and renal function. After a 5-day recovery period, sepsis was induced via continuous intravenous infusion of live Escherichia coli for 30 hours. After 24 hours, the sheep were randomized to receive an intravenous infusion of 3.6 pmol/kg/min GLP-1 (n = 8) or a fluid-matched vehicle (n = 8) for 6 hours. Results After 24 hours of sepsis, 7/8 sheep in each group developed oliguria, which was consistent with the criteria for AKI. Compared with vehicle, GLP-1 significantly increased renal blood flow (p = 0.0054), renal oxygen delivery (p = 0.0032), and renal cortical oxygenation (p < 0.001) and improved renal medullary perfusion (p = 0.029) during the intervention period. However, GLP-1 did not significantly improve the primary endpoint of renal medullary oxygenation (p = 0.115). Conclusion In an ovine model of gram-negative sepsis-associated AKI, GLP-1 infusion improved global renal perfusion, renal oxygen delivery, and cortical oxygenation but failed to improve renal medullary oxygenation and kidney function.