title: Development of intestinal ischemia/reperfusion-induced acute kidney injury in rats with or without chronic kidney disease: Cytokine/chemokine response and effect of α-melanocyte-stimulating hormone.
abstract: BACKGROUND
  The primary aim of the study was to investigate the cytokine/chemokine response in the kidney, lung, and liver following acute kidney injury (AKI). The secondary aim was to test whether α-melanocyte-stimulating hormone (α-MSH) could prevent a reduction in organ function, and attenuate the inflammatory cytokine/chemokine response within the kidney, lung, and liver following AKI in rats with or without preexisting chronic kidney disease (CKD).
  
  
  METHODS
  A two-stage animal model, in which AKI was induced in rats with preexisting CKD, induced by 5/6 nephrectomy (Nx), was used. Six weeks later, AKI was induced by intestinal ischemia and reperfusion (IIR). Sham procedures [S(Nx) and S(IIR)] were also performed.
  
  
  RESULTS
  Increasing levels of serum creatinine (sCr) demonstrated progressive development of CKD in response to Nx, and following IIR sCr levels increased further significantly, except in the S(Nx) group treated with α-MSH. However, no significant differences in the fractional increase in sCr were observed between any of the groups exposed to IIR. In kidney, lung, and liver tissue the levels of interleukin (IL)-1β were significantly higher in rats undergoing IIR when compared to the S(IIR) and control rats. The same pattern was observed for the chemokine monocyte chemoattractant protein (MCP)-1 in lung and liver tissue. Furthermore, kidney IL-1β and RANTES levels were significantly increased after IIR in the Nx rats compared to the S(Nx) rats.
  
  
  CONCLUSIONS
  Both the functional parameters and the cytokine/chemokine response are as dramatic when AKI is superimposed onto CKD as onto non-CKD. No convincing protective effect of α-MSH was detected.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark; The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Skott
authors.affiliation: The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark; Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.affiliation: Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Birke-Sørensen
authors.affiliation: Research Unit for Molecular Medicine, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Palmfeldt
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jonassen
authors.affiliation: The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark; Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiær
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark; The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
keywords: Acute kidney injury; Chronic kidney disease; Intestinal ischemia and reperfusion; α-melanocyte-stimulating hormone