Reduced Inflammatory Response of the Brain Dead Kidney Graft with Nyk pre-treatment.

Kloeze, J.H. (Jurian Harm) (2014) Reduced Inflammatory Response of the Brain Dead Kidney Graft with Nyk pre-treatment. thesis, Medicine.

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Abstract

Introduction Kidney transplantation is ultimately needed for end-stage renal failure patients to maintain life. Short-term and long-term outcomes are higher with living kidney donation compared to heart-beating (HB) kidney donation. The discrepancy cannot be explained with differences in human leukocyte antigen difference or ischemia times. Comparisons between living kidney grafts and HB kidney grafts revealed that HB kidney grafts are inflammatory active at the time of donation. The inflammatory state induces histological damage, which enhanced ischemia/reperfusion injury in the recipient. Described here is a first attempt with pre-treatment of geranyl-geranylacetone (GGA)-derivate Nyk, to test if it can reduce the inflammatory active state in the kidney from HB donors via heat shock protein (HSP)-72 and heme oxygenaze (HO)-1 expression. Material and methods A graduate onset brain death model was used with male Fischer rats (N=36) to analyze the inflammatory and protective response of the kidney to brain death. Rats were divided in three groups: Nyk, GGA, and Saline. Inflammatory parameters were adhesion molecules E-selectin, Intracellular adhesion molecule (Icam)-1, and neutrophil and monocyte/macrophage infiltration. Results A decreased up-regulation of E-selectin, Icam-1, and subsequent infiltration of neutrophil was seen after Nyk pre-treatment compared to GGA or Saline pre-treatment. HSP-72 showed broad expression with Nyk pre-treatment compared to low expression of GGA and Saline pre-treatment. HO-1 expression was low in all pre-treated HB animals. Conclusion A reduced renal inflammatory response was seen with Nyk pre-treatment in brain dead rats compared to GGA or Saline pre-treatment. Nyk did not induce a significant higher expression of HSP-72 or HO-1. Other HSPs should therefore be analyzed to understand how Nyk pre-treatment reduces the renal inflammatory response. Short-term outcomes should be analyzed with ischemia/reperfusion experiments.

Item Type:	Thesis (Thesis)
Supervisor name:	Leuvenink, Dr. H.G.D. and Dullemen, L.F.A. van
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:38
Last Modified:	25 Jun 2020 10:38
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/34

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