Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date

<jats:title>Abstract</jats:title><jats:p>The longest survival of a non‐human primate with a life‐supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an α‐1,3‐galactosyltransferase gene‐knockout pig transgenic for two human complement‐regulatory proteins and three human coagulation‐regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with <jats:styled-content style="fixed-case">ATG</jats:styled-content>+anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>20mAb (induction) and anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>40mAb+rapamycin+corticosteroids (maintenance). Anti‐<jats:styled-content style="fixed-case">TNF</jats:styled-content>‐α and anti‐<jats:styled-content style="fixed-case">IL</jats:styled-content>‐6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein‐losing nephropathy were observed. There was no evidence of an elicited anti‐pig antibody response. Death was from septic shock (<jats:italic>Myroides</jats:italic> spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti‐inflammatory agents prevented immune injury and a protein‐losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.</jats:p>