Dexmedetomidine Might Exacerbate Acute Kidney Injury, While Midazolam Might Have a Postconditioning Effect: A Rat Model of Lipopolysaccharide-Induced Acute Kidney Injury

Background: The preconditioning effects of dexmedetomidine and propofol on septic acute kidney injury (AKI) have been reported, but the postconditioning effects remain unknown. This study investigated the postconditioning effects of dexmedetomidine, midazolam, and propofol on septic AKI. Methods: Forty-eight male Wistar rats were intraperitoneally administered lipopolysaccharide (LPS; 8.3 mg kg-1) or normal saline. Twenty-four hours later, rats were allocated to specific anesthetic groups (n=6 each) and exposed for 6 h, as follows: C, control (no anesthetic); D, dexmedetomidine (5 μg kg-1 h-1); M, midazolam (0.6 mg kg-1 h-1); or P, propofol (10 mg kg-1 h-1). Serum creatinine (Cr) and cystatin C (CysC) were measured at the end of anesthesia. Western blot and immunofluorescent analyses of kidney samples were performed. Results: Among LPS-treated groups, D group showed worsened renal dysfunction (L-C vs L-D: Cr, P=0.002, effect size (η2) =0.83; CysC, P=0.004, η2=0.71), whereas M group showed improved renal function (L-C vs L-M: Cr, P=0.009, η2=0.55). In immunofluorescent analysis of renal tubules, D group showed increased expression of nuclear factor κB (NFκΒ) (L-C vs L-D: NFκΒ, P=0.002, η2=0.75; phospho-NFκΒ, P=0.018, η2=0.66) and inhibitor of κ light polypeptide gene enhancer in B-cell kinase β (IKKβ) (L-C vs L-D: IKKβ, P=0.002, η2=0.59; phospho-IKKα/β, P=0.004, η2=0.59), whereas M group showed decreased NFκB expression (L-C vs L-M: NFκB, P=0.003, η2=0.55; phospho-NFκB, P=0.013, η2=0.46). Conclusions: Dexmedetomidine administration might worsen septic AKI, while midazolam might preserve kidney function via the NFκΒ pathway.