Details

Autor(en) / Beteiligte

• Schuurs, T. A.
• Morariu, A. M.
• Ottens, P. J.
• 't Hart, N. A.
• Popma, S. H.
• Leuvenink, H. G. D.
• Ploeg, R. J.

Titel

Time‐Dependent Changes in Donor Brain Death Related Processes

Ist Teil von

• American journal of transplantation, 2006-12, Vol.6 (12), p.2903-2911

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2006

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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, Il‐6) were massively up‐regulated (p < 0.05) already 0.5 h after BD. Inducers of proinflammatory gene expression were either activated (NF‐κB) 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. The brain‐death‐induced proinflammatory response, as demonstrated in rat brain‐dead donor kidneys, develops rapidly (within 0.5 h after brain death induction) and may be initiated by MCP‐1 and/or KC‐protein.