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BACKGROUND: After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation. METHODS: Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients. RESULTS: In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors. CONCLUSIONS: E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.

Original publication

DOI

10.1016/j.transproceed.2004.12.262

Type

Conference paper

Publication Date

01/2005

Volume

37

Pages

367 - 369

Keywords

Biopsy, Brain Death, Chemokine CCL2, E-Selectin, Follow-Up Studies, Gene Expression Regulation, HSP70 Heat-Shock Proteins, Heme Oxygenase (Decyclizing), Heme Oxygenase-1, Humans, Immunohistochemistry, Inflammation, Kidney Transplantation, Living Donors, Membrane Proteins, Nephrectomy, Reverse Transcriptase Polymerase Chain Reaction, Tissue Donors, Tissue and Organ Harvesting, Transforming Growth Factor beta, Treatment Outcome