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Kidney Week

Abstract: SA-PO187

Effects of Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) on Renal Vascular Reactivity in Cirrhotic Rats

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Chuang, Chiao-Lin, Taipei Veterans General Hospital, Taipei, Taiwan
  • Huang, Hui-Chun, Taipei Veterans General Hospital, Taipei, Taiwan
Background

Variceal bleeding-associated hypotension may activate endogenous vasoconstrictors, leading to renal vasoconstriction and subsequent acute kidney injury (AKI) in cirrhotic patients.
Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a new class of oral anti-hyperglycemic drugs with pleiotropic effects. In addition to the reductions in blood pressure and body weight, SGLT2i showed improvements in renal outcomes. The possible mechanisms included inhibition of inflammation and oxidative stress and a reduction in glomerular hyperfiltration via afferent arteriolar vasoconstriction. Cirrhotic kidney has the same picture of renal hyperfiltration with diabetic kidney. Therefore, the renoprotective role of SGLT2i in cirrhotic kidneys is worth evaluating.

Methods

Liver cirrhosis was induced in S-D rats with common bile duct ligation (CBDL). Rats received oral distill water or SGLT2i (Empagliflozin, 30 mg/kg/day) for 28 days. On the 28th day, AKI was induced by ischemic-reperfusion injury (IRI). On the 29th day, the following was investigated: (a) hemodynamic parameters, (b) serum glucose, BUN, Cr, ALT, AST, IL-1, IL-6, TNF-α , (d) in-situ kidney perfusion, (e) oxidative stress and western analysis of kidneys.

Results

SGLT2i treatment showed no significant change in serum parameters, but lower TNF-α (p < 0.05) in CBDL rats. Renal IRI enhanced renal vascular reactivity to endothelin-1 (ET-1) and led to significant increases in serum BUN and Cr (all p < 0.05), suggesting AKI. Compared with DW-treated rats, SGLT2i treatment abrogated IRI-related renal vascular hyper-reactivity to ET-1 (Fig) and showed lower BUN and Cr following IRI (all p < 0.05). The exact mechanisms of renal protection remained under analysis.

Conclusion

In conclusion, our results demonstrated beneficial effects of SGLT2i in kidneys of CBDL rats, including reduced inflammation, abrogated IRI-related renal vascular hyper-reactivity to vasocontrictor, and protection from AKI. Therefore, SGLT2i might be recommended for cirrhotic patients.

Fig. IRI increased renal vascular response to ET-1 in CBDL rats (A). SGLT2i treatment abrogated renal vascular hyper-reactivity to ET-1 following IRI (B).