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.

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 α-MSH was detected.

• Authors: Martin Skott, Rikke Nørregaard, Hanne Birke-Sørensen, Johan Palmfeldt, Tae-Hwan Kwon, Thomas Jonassen, Jørgen Frøkiær, Søren Nielsen
• Journal: Kidney research and clinical practice (Kidney Res Clin Pract) Vol. 33 Issue 2 Pg. 79-88 (Jun 2014) ISSN: 2211-9132 [Print] Korea (South)
• PMID: 26877955 (Publication Type: Journal Article)