Accelerated rejection of renal allografts from brain-dead donors

Objective To define the potential influences of donor brain death on organs used for transplantation. Summary Background Data Donor brain death causes prompt upregulation of inflammatory mediators on p eripheral organs. It is hypothesized that this antigen-independent insult m ay influence the rate and intensity of host alloresponsiveness after engraf tment. Methods The rates of survival of unmodified Lew recipients sustained by kidney allo grafts from brain-dead, normal anesthetized, and anesthetized ventilated F3 44 donors were compared. Brain death was induced by gradually increasing in tracranial pressure under electroencephalographic control. Tracheotomized b rain-dead animals and anesthetized controls were mechanically ventilated fo r 6 hours before transplant nephrectomy. The rate and intensity of the acut e rejection event were examined by histology, immunohistology, and reverse transcriptase-polymerase chain reaction. Results Animals bearing kidneys from brain-dead donors died of renal failure second ary to acute rejection at a significantly faster rate than those from anest hetized living controls or anesthetized animals ventilated for 6 hours. Wit hin 3 hours after placement and reperfusion of brain-dead donor grafts, sig nificant neutrophil infiltration was observed, followed by increasing numbe rs of macrophages and T cells. mRNA of proinflammatory mediators detected i n kidneys within 6 hours of brain death and upregulated even before transpl antation increased thereafter and appeared to accelerate and amplify host a lloresponsiveness, as manifested by the rapid expression of chemokines, cyt okines, adhesion molecules, and major histocompatibility complex class II a ntigens in the engrafted organ. The process evolved in the controls less in tensely and at a slower rate. Conclusions Donor brain death is a significant risk factor for peripheral organs used f or transplantation. The activated state of such organs appears to trigger h ost immune mechanisms that accelerate the process of acute rejection. The e ffects of this central injury may explain in part the less satisfactory per formance of cadaver organs in human transplantation compared with those fro m living sources.