title: Glucocorticoids attenuate septic acute kidney injury.
abstract: BACKGROUND
  The incidence and mortality of septic acute kidney injury (AKI) remains high, whereas our understanding of pathogenesis for septic AKI is still limited. Glucocorticoids (GCs) have been clinically recommended for treatment of septic shock and also have showed favorable effect on septic AKI in several animal experiments. The aim of this study is to investigate the pathophysiology of septic AKI and the effect of GCs on septic AKI.
  
  
  METHODS
  We induced septic AKI using cecal ligation and puncture (CLP) model in 8-10 wk-old male C57BL/6 mice. Saline or dexamethasone (2.5 mg/kg) dissolved in saline was administered after surgery. Hemodynamic, biochemical and histological changes were examined in a time-course manner.
  
  
  RESULTS
  CLP resulted in hyperdynamic warm shock with multiple organ dysfunction including AKI. Despite renal dysfunction, light microscopy showed scanty acute tubular necrosis and inflammation. Instead, CLP induced significant increase in apoptosis of the kidney and spleen cells. In addition, septic kidneys showed mitochondrial injury and alterations in Bcl2 family proteins in the renal tubular cells. Dexamethasone treatment attenuated renal dysfunction, but it was not associated with improvement of hemodynamic parameters. Dexamethasone-induced organ protective effect was associated with reduced mitochondrial injury with preserved cytochrome c oxidase and suppression of proapoptotic proteins as well as reduced cytokine release.
  
  
  CONCLUSIONS
  Mitochondrial damage and subsequent apoptosis are thought to play important role in the development of septic AKI. GCs might be a useful therapeutic strategy for septic AKI by reducing mitochondrial damage and apoptosis.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Choi
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Eunjung
authors.initials: E
authors.lastname: Cho
authors.forename: Young Youl
authors.initials: YY
authors.lastname: Hyun
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Cha
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Cho
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects*; D018805:Sepsis / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids