Kidney Res Clin Pract.  2014 Jun;33(2):79-88.

Development of intestinal ischemia/reperfusion-induced acute kidney injury in rats with or without chronic kidney disease: Cytokine/chemokine response and effect of alpha-melanocyte-stimulating hormone

• Skottx M
• Norregaard R
• Birke-Sorensen H
• Palmfeldt
• Kwon TH
• Jonassen T
• Frokiaer J
• Nielsen S

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 alpha-melanocyte-stimulating hormone (alpha-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 alpha-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)-1beta 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-1beta and RANTES levels were significantly increased after IIR in the Nx rats compared to the S(Nx) rats.
CONCLUSION
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 alpha-MSH was detected.

Keyword

Acute kidney injury; Chronic kidney disease; Intestinal ischemia and reperfusion; alpha-melanocyte-stimulating hormone

MeSH Terms

Acute Kidney Injury*
alpha-MSH*
Animals
Chemokine CCL5
Creatinine
Interleukins
Ischemia
Kidney
Liver
Lung
Models, Animal
Monocytes
Nephrectomy
Rats*
Renal Insufficiency, Chronic*
Reperfusion
Chemokine CCL5
Creatinine
Interleukins
alpha-MSH