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

## TL;DR

This study tested if GLP-1 helps protect the kidneys in sheep with sepsis-related kidney injury, finding some benefits but not full improvement.

## Contribution

The study is the first to investigate GLP-1's effects on kidney oxygenation and function in a sheep model of sepsis-associated AKI.

## Key findings

- GLP-1 increased renal blood flow and improved cortical oxygenation in septic sheep.
- GLP-1 did not significantly improve renal medullary oxygenation or overall kidney function.
- Both groups developed AKI, but GLP-1 showed partial renoprotective effects.

## Abstract

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. 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 h. After 24 h, 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 h. After 24 h of sepsis, 7/8 sheep in each group developed AKI. GLP-1 treatment increased renal blood flow compared to placebo + 13 vs. − 3.4 ml/min difference (95% CI) = 16 (− 7–40) P = 0.0054), and maintained renal cortical oxygenation + 2.5 mmHg vs. = − 7.2 mmHg, difference (95% CI) = 9.7 (5.2–14.4) P < 0.001. GLP-1 maintained renal medullary perfusion + 1.7 vs. vehicle − 213 perfusion units, difference (95% CI) = 214 (− 21–450) P = 0.07. However, GLP-1 did not significantly improve the primary endpoint of renal medullary oxygenation − 1.6 vs. − 11.5, difference (95% CI) = 9.9 (− 6.8–26.7) P = 0.21. In an ovine model of gram-negative sepsis-associated AKI, GLP-1 infusion supported global renal perfusion, renal oxygen delivery, and cortical oxygenation but failed to improve renal medullary oxygenation and kidney function.

The online version contains supplementary material available at 10.1038/s41598-025-33109-0.