title: Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model.
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.
  
  
  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.
authors: 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.
authors: Chieko
authors: C
authors: Mitaka
authors: Intensive Care Unit, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Masuda
authors: Department of Anesthesiology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors: Koji
authors: K
authors: Kido
authors: Department of Anesthesiology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors: Tokujiro
authors: T
authors: Uchida
authors: Department of Comprehensive Pathology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors: Shinya
authors: S
authors: Abe
authors: Laboratory of Animal Biological Responses, Department of Veterinary Science School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
authors: Taku
authors: T
authors: Miyasho
authors: Clinical Research Center, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan.
authors: Makoto
authors: M
authors: Tomita
authors: Department of Anesthesiology, Juntendo University Hospital, Tokyo, Japan.
authors: Eiichi
authors: E
authors: Inada
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006464:Hemoperfusion; D008297:Male; D011112:Polymyxin B / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications*
chemical_list: D000900:Anti-Bacterial Agents; D011112:Polymyxin B
keywords: Acute kidney injury; Apoptosis; Cecal ligation and puncture; Cytokines; NF-κB; Poly (ADP-ribose) polymerase