The influence of warm ischemia elimination on kidney injury during transplantation - clinical and molecular study

Abstract

Kidney surface cooling was used during implantation to assess the effect of warm ischemia elimination on allograft function, histological changes and immune-related gene expression. 23 recipients were randomly assigned to a group operated on with kidney surface cooling during implantation (ice bag technique, IBT group), and the other 23 recipients receiving the contralateral kidney from the same donor were operated on with a standard technique. Three consecutive kidney core biopsies were obtained during the transplantation procedure: after organ recovery, after cold ischemia and after reperfusion. Gene expression levels were determined using low-density arrays (Format 32, TaqMan). The IBT group showed a significantly lower rate of detrimental events (delayed graft function and/or acute rejection, p = 0.015) as well as higher glomerular filtration rate on day 14 (p = 0.026). A greater decrease of MMP9 and LCN2 gene expression was seen in the IBT group during total ischemia (p = 0.003 and p = 0.018). Elimination of second warm ischemia reduced the number of detrimental events after kidney transplantation, and thus had influence on the short-term but not long-term allograft function. Surface cooling of the kidney during vascular anastomosis may reduce some detrimental effects of immune activation resulting from both brain death and ischemia-reperfusion injury.

Figure 1. Gene expression presented as ΔΔCt (dot-median, line-interquartile range).

Data presented for each of the three biopsies (B1-light gray, B2-dark grey, B3-black).

Figure 2. The change in MMP9 and LCN2 gene expression levels over ischemia time in matched pairs of the kidneys from the same donor as observed in IBT (grey box) vs ST group (white box).

Data presented as median (horizontal line), interquartile range (box), and values range (vertical line).