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- Title
Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.
- Authors
Hulst, Abraham H.; Ow, Connie P. C.; May, Clive N.; Hood, Sally H.; Plummer, Mark P.; Hermanides, Jeroen; van Raalte, Daniël H.; Deane, Adam M.; Bellomo, Rinaldo; Lankadeva, Yugeesh R.
- Abstract
Background: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI. Methods: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8). Results: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes. Conclusion: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.
- Subjects
EMPAGLIFLOZIN; ACUTE kidney failure; KIDNEY physiology; OXYGEN in the blood; SODIUM-glucose cotransporter 2 inhibitors; TYPE 2 diabetes
- Publication
Intensive Care Medicine Experimental, 2024, Vol 12, Issue 1, p1
- ISSN
2197-425X
- Publication type
Article
- DOI
10.1186/s40635-024-00647-2