LIFE-SUPPORTING PIG-TO-PRIMATE RENAL XENOTRANSPLANTATION USING GENETICALLY-MODIFIED DONORS

Background. In order to circumvent the complement-mediated Hyperacute rejection of discordant xenografts, a colony of pigs transgenic for th e human regulator of complement activity, human decay-accelerating fac tor (hDAF), has been produced, Methods. Seven kidneys from hDAF transg enic pigs and six kidneys from nontransgenic control pigs were transpl anted into cynomolgus monkeys; both native kidneys were removed during the same operation, The recipient animals were immunosuppressed with cyclosporine, steroids, and cyclophosphamide. Results. In the transgen ic group, the median survival time was 13 days (range, 6-35 days); the median survival time in the control group was 6.5 days (range, 0.3-30 days). There were no cases of hyperacute rejection in the transgenic group, and the two longest-surviving kidneys in this group showed no e vidence of rejection ore histological examination, In contrast, all co ntrol kidneys underwent antibody-mediated rejection, one demonstrating hyperacute rejection and the others acute vascular rejection, Conclus ion. This study demonstrates that (i) a kidney from an hDAF transgenic pig can support the life of a primate for up to 35 days (and also sho ws the basic physiological compatibility between the pig and nonhuman primate); (ii) nontransgenic kidneys are not routinely hyperacutely re jected; and (iii) the presence of hDAF on the kidney confers some prot ection against acute vascular rejection. Improved immunosuppression an d immunological monitoring may enable extended survival.