Issn Print: 0041-1337

Publication Date: 2001/06/15


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The Contribution of Adhesion Molecule Expression in Donor Kidney Biopsies to Early Allograft Dysfunction. Transplantation 2001: 71: 1666.

Schwarz C; Regele H; Steininger R; Hansmann C; Mayer G; Oberbauer R

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Excerpt

Long-term graft survival of cadaver renal allografts has been shown to be inferior to that of living donor transplantation. This may be partly attributed to living donor kidneys being optimally obtained from healthy individuals with minimal ischemia times, whereas cadaver kidneys may have experienced injury due to a variety of traumatic events leading up to brain death. There is increasing evidence to suggest that injury to cadaver donor kidneys may increase their susceptibility to early inflammatory responses such as ischemia/reperfusion injury and acute rejection. Both delayed graft function and early acute rejection have been identified as highly significant risk factors affecting long-term allograft survival. Indeed, a synergistic adverse effect on graft survival has been observed in renal allografts experiencing both delayed graft function and acute rejection. Although delayed graft function is significantly affected by prolonged cold preservation of kidneys, most probably through damage caused by ischemia/reperfusion injury, donor-related risk factors remain to be identified that may predispose certain cadaver renal allografts to early graft dysfunction or acute rejection.
In this issue of Transplantation, Schwarz and colleagues report on an investigation into the potential effects of cadaver donor kidney injury and the impact on subsequent graft outcome. They have demonstrated that cadaver kidneys express high levels of the proinflammatory adhesion molecules ICAM-1, VCAM-1, and E-selectin compared with living donor kidneys, confirming previously established observations (1). Up-regulation of these adhesion molecules involved in leukocyte recruitment did not appear to be associated with the incidence of acute rejection following transplantation, but high levels of ICAM-1 were significantly associated with delayed graft function. Nevertheless elevated expression of ICAM-1 was not a specific marker for delayed graft function as it was also detected in donor kidneys with good primary function after transplantation. We have previously demonstrated a significant association between high levels of cadaver donor kidney adhesion molecule expression and early acute rejection episodes in the transplant, but again, this was not a specific marker for acute rejection as high levels of adhesion molecules before transplantation were detected in the absence of early acute rejection episodes (1). Although the expressions of adhesion molecules on the endothelium and tubular epithelia may not be specific markers of either graft dysfunction or rejection, it is highly probable that they contribute significantly to early posttransplant inflammatory events by recruiting recipient leukocytes that may mediate ischemia/reperfusion injury and/or acute rejection.
Thus, the question arises as to which factors may cause increased levels of adhesion molecule expression in cadaveric, but not living donor kidneys. Adhesion molecules have been shown to be up-regulated on endothelial and proximal tubular epithelial cells by a variety of inflammatory stimuli. In cadaveric donors the organs may experience inflammatory events as a result of severe traumatic injury, instability of vital functions and drug management in intensive care, ischemia/reperfusion injury, episodes of infection, and the physiological abnormalities observed during and after brain death. In marked contrast, kidneys obtained from healthy, carefully screened living donors with no preexisting history of organ or tissue damage may be considered normal. We have demonstrated that elevated adhesion molecule expression in cadaveric kidneys was significantly associated with traumatic injury, length of ventilation, episodes of infection, and administration of desmopressin (1). These factors may induce cytokine gene expression within donor tissues, indeed Kim and colleagues have recently demonstrated high levels of inflammatory cytokine gene expression in pretransplant cadaveric kidneys, equivalent to the levels detected in biopsies obtained during episodes of acute rejection, and significantly higher than the levels found in living donor kidneys (2).
There is mounting evidence from animal studies showing that brain death itself may result in damage to the organs.
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