Improvements in early behavior of rat kidney allografts after treatment ofthe brain-dead donor

Objective To improve the quality of organs from brain-dead donors by assess ing the influence of alternative strategies on the early behavior of kidney s after transplantation into unmodified hosts. Summary Background Data Kidneys transplanted from living donors perform con sistently better than those from cadaver sources. The authors have recently shown that donor brain death produces inflammatory changes in peripheral o rgans within hours, amplifies coincident ischemia-reperfusion injury, and a ccelerates acute and chronic rejection. Normalization of the graft by donor hormone treatment has hitherto been unsuccessful. Methods A standardized rat model of brain death was used. Experimental grou ps included recipients of allogeneic grafts from living and brain-dead dono rs (F344 --> LEW). Donors were treated immediately after induction of brain death either with intravenous steroids, which block inflammatory cytokine release, or a soluble P-selectin glycoprotein ligand (sPSGL), which blocks initial selectin-mediated cellular adhesion. Kidney grafts were examined se rially up to 10 days by morphology, immmunohistology, and reverse transcrip tase-polymerase chain reaction. Results Overall survival of ummodified recipients of kidneys from brain-dea d donors was significantly reduced versus living donors. Animals with organ s from brain-dead donors that had received steroids or sPSGL survived signi ficantly longer than those from untreated brain-dead donors. The intensity of ischemia-reperfusion injury and of acute rejection was reduced. Cellular infiltration and transcription of mRNA of representative proinflammatory m ediators were diminished. Conclusions Treatment of organ donors at the time of brain death markedly i mproves organ quality after kidney transplantation, upgrading it to that fr om a living donor.