Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts

Background. Recently, there has been a resumed interest in clinical xenotra nsplantation using pig organs, However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month, We have attempted to obtain long-term survival of nonhuman pr imates using human decay-accelerating factor (hDAF) transgenic pig organs a nd an immunosuppressive strategy particularly aimed at neutralizing the hum oral component of the immune response. Methods, hDAF transgenic or control kidneys were transplanted into 14 bilat erally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwe nt splenectomy and mere immunosuppressed with cyclosporine A, cyclophospham ide, and steroids, All animals also received recombinant erythropoietin, Po stoperatively, the primates were monitored daily. Laboratory evaluations in cluded serum biochemistry, hematology, and measurements of hemolytic antipi g antibodies. To assess the role of splenectomy in the control of humoral r esponse, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin, Results, This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porci ne renal xenograft, Furthermore, four of nine animals in this series surviv ed for 50 days or more. Most biochemical measurements in this study (includ ing plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving ani mals. Conclusions. Normalization of renal function (urea and creatinine) in prima te recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppress ive approaches, specifically designed to prevent humorally mediated immunol ogical damage, should be explored to further prolong survival of primates t hat have received porcine xenografts.