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

Department Anesthesiology Nippon Tokyo, Japan Background: The preconditioning effects of dexmedetomidine and propofol on septic acute kidney in-jury (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 mu g 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 (eta 2)=0.83; CysC, P=0.004, eta 2=0.71), whereas M group showed improved renal function (L-C vs L-M: Cr, P=0.009, eta 2=0.55). In immunofluorescent analysis of renal tubules, D group showed in-creased expression of nuclear factor kappa B (NF kappa Beta) (L-C vs L-D: NF kappa Beta, P=0.002, eta 2=0.75; phospho-NF kappa Beta, P= 0.018, eta 2=0.66) and inhibitor of kappa light polypeptide gene enhancer in B-cell kinase beta (IKK beta) (L-C vs L-D: IKK beta, P=0.002, eta 2=0.59; phospho-IKK alpha/beta, P=0.004, eta 2=0.59), whereas M group showed decreased NF kappa B expression (L-C vs L-M: NF kappa B, P=0.003, eta 2=0.55; phospho-NF kappa B, P=0.013, eta 2=0.46).Conclusions: Dexmedetomidine administration might worsen septic AKI, while midazolam might pre-serve kidney function via the NF kappa Beta pathway. (J Nippon Med Sch 2023; 90: 387 & horbar;397)