Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model

Chieko Mitaka; Takahiro Masuda; Koji Kido; Tokujiro Uchida; Shinya Abe; Taku Miyasho; Makoto Tomita; Eiichi Inada

doi:10.1016/j.jss.2015.10.020

Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model

J Surg Res. 2016 Mar;201(1):59-68. doi: 10.1016/j.jss.2015.10.020. Epub 2015 Nov 10.

Authors

Chieko Mitaka¹, Takahiro Masuda², Koji Kido³, Tokujiro Uchida³, Shinya Abe⁴, Taku Miyasho⁵, Makoto Tomita⁶, Eiichi Inada⁷

Affiliations

¹ Department of Anesthesiology, Juntendo University Hospital, Tokyo, Japan; Department of Anesthesiology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan. Electronic address: c-mitaka@juntendo.ac.jp.
² Intensive Care Unit, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan.
³ Department of Anesthesiology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
⁴ Department of Comprehensive Pathology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
⁵ Laboratory of Animal Biological Responses, Department of Veterinary Science School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
⁶ Clinical Research Center, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan.
⁷ Department of Anesthesiology, Juntendo University Hospital, Tokyo, Japan.

PMID: 26850185
DOI: 10.1016/j.jss.2015.10.020

Abstract

Background: Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood.

Materials and methods: Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections.

Results: PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P < 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P < 0.001) attenuated the expressions of cleaved PARP and NF-κB p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP.

Conclusions: These findings suggest that PMX-DHP may protect against acute kidney injury not only by inhibiting the NF-κB signaling pathway but also by preventing renal tubular cell apoptosis.

Keywords: Acute kidney injury; Apoptosis; Cecal ligation and puncture; Cytokines; NF-κB; Poly (ADP-ribose) polymerase.

MeSH terms

Acute Kidney Injury / etiology
Acute Kidney Injury / prevention & control*
Animals
Anti-Bacterial Agents / therapeutic use*
Disease Models, Animal
Drug Evaluation, Preclinical
Hemoperfusion*
Male
Polymyxin B / therapeutic use*
Rats, Sprague-Dawley
Sepsis / complications*

Substances

Anti-Bacterial Agents
Polymyxin B