Xenotransplantation of human decay accelerating factor transgenic porcine kidney to non-human primates: 4 years experience at a Canadian center.

From July 1999 to December 2002, a total of 27 baboons underwent transplantation with human decay accelerating factor (hDAF) transgenic porcine kidneys. The immunosuppressive protocol included combinations of 1 or more of the following immunosuppressive agents: cyclosporine, TPC, cyclosphophamide, methylprednisolone, GAS914 (a polymeric alpha-Gal), rabbit antithymocyte serum (RATS), and rapamycin derivative (RAD). The animals were followed up clinically with monitoring of renal function based on daily creatinine and urinary output. Histopathological examination of the tissue samples was performed after paraffin embedding. Electron microscopy was performed on occasion. All pathology was read blindly with a semiquantitative scoring method to assess the presence or absence of histological features of xenotransplant rejection. Mean survival time was 20.7 days (range, 4-75 days) with 15 animals dying of classic humoral rejection and 12 dying of complications unrelated to rejection. The most frequent complications were as follows: chronic diarrhea with malabsorption, bleeding diathesis, infections, and drug toxicity. Irrespective of the immunosuppressive regimen, a significant number of baboons (10) developed untreatable diarrhea and gastrointestinal bleeding. Samples of their gastrointestinal tracts showed evidence of varying degrees of necrotizing vasculitis with immunoglobulin (Ig)G,IgM, and fibrin deposition. The survival in pig-to-baboon kidney xenotransplantation continues to be limited by acute xenograft rejection and complications of immunosuppression. Although significantly increased survivals have been obtained, an ideal protocol has not yet been achieved. Efforts will continue in an attempt to develop a protocol with minimal complications and long-term survival beyond 90 days.