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Donor brain death (BD) affects kidney function and survival after transplantation. Studies on brain dead kidney donors indicate that, besides inflammation and coagulation, cytoprotective gene expression is activated as well. Here, we evaluated in a time-course experiment progression of these renal BD-related processes. Animals were sacrificed 0.5, 1, 2 or 4 h after BD and compared to sham-operated controls. Proinflammatory genes (E-selectin, MCP-1, II-6) were massively up-regulated (p < 0.05) already 0.5 h after BD. Inducers of proinflammatory gene expression were either activated (NF-kappaB) or induced in expression (Egr-1) after 0.5 h of BD. Increased numbers of infiltrating granulocytes were seen in the interstitium from 0.5 h on. Also, expression of protective genes HO-1 and HSP70 were increased within 0.5 h. Remarkably, reactive oxygen species formation was detectable only in the later phase of BD. Among 14 measured serum cytokines, MCP-1 and KC-protein were significantly elevated from 0.5 h on. In conclusion, a fast induction of proinflammatory and stress-induced protective processes in brain dead donor kidneys was demonstrated, probably triggered by changes occurring during BD induction. Importantly, hypoxia appeared not to be one of the initial triggers, and early increased systemic levels of chemokines MCP-1 and KC may be regarded as the starting point for the inflammatory cascade in brain dead donor kidneys.

Original publication

DOI

10.1111/j.1600-6143.2006.01547.x

Type

Journal article

Journal

Am J Transplant

Publication Date

12/2006

Volume

6

Pages

2903 - 2911

Keywords

Animals, Brain Death, Cytokines, DNA Primers, Family, Inflammation, Kidney, Kidney Transplantation, Kinetics, Models, Animal, Oxidative Stress, Polymerase Chain Reaction, Postmortem Changes, Rats, Rats, Inbred F344, Time Factors, Tissue Donors