-Original-

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

Akiko Hata, Makiko Yamamoto, Masae Iwasaki, Tomonori Morita, Masashi Ishikawa and Atsuhiro Sakamoto

Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

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.

J Nippon Med Sch 2023; 90: 387-397

Keywords
acute kidney injury, dexmedetomidine, lipopolysaccharide, midazolam, sepsis

Correspondence to
Akiko Hata, Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
s11-113wa@nms.ac.jp

Received, November 28, 2022
Accepted, April 17, 2023