Duration of Brain Death and Cold Ischemia Time, But Not Warm Ischemia Time, Increases Expression of Genes Associated With Apoptosis in Transplanted Kidneys From Deceased Donors

Apoptosis is one of the most important mechanisms leading to kidney graft injury during transplantation. The aim of this study was to assess the expression of genes involved in apoptosis in transplanted kidneys derived from deceased donors (DD) at various stages of the transplant procedure, seventy eight transplanted kidneys procured from 43 DD were included in this study. As a baseline control for gene expressions we used six kidney allografts obtained from living donors (LD). Three core biopsies were performed: biopsy 1-5 minutes before organ perfusion in the donor; biopsy 2 at the end of cold ischemia before kidney implantation; and biopsy 3-30 minutes after reperfusion. Tumor protein p53 (TP53), caspase-3 (CASP3), B-cell lymphoma 2 protein (Bcl2), and heme oxygenase 1 (HO-1) gene expression levels were determined using custom-designed low-density arrays (TaqMan assay). Comparison of gene expression between DD and LD kidneys revealed greater expression of all genes in kidneys from DD in all biopsies; however, only CASP3 expression in biopsy 1 and TP53 expression in biopsy 3 were statistically significant. Prolongation duration of brain death beyond 10 hours in DD resulted in a significantly decreased CASP3 expression in biopsy 1. When the cold ischemia time (CIT) was longer than 24 hours, the expressions of Bcl2, TP53, and CASP3 were significantly higher compared to kidneys with ClT < 24 hours. There was no correlation between warm ischemia time and gene expression in biopsy 3. CASP3 and TP53 expression only in biopsy 1 were significantly higher among kidney allografts with delayed (DGF) compared with immediate graft function. In conclusion expression of genes involved in apoptosis was more pronounced in kidney allografts from deceased donors. A prolonged donor brain-death period beyond 10 hours resulted in decreased CASP3 expression. CIT longer than 24 hours was associated with increased expressions of Bcl2, TP53, and CASP3. CASP3 and TP53 expressions were significantly higher among kidneys allografts displaying DGF.