title: Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.
abstract: 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 ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-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 (Myroides 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.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.|Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wijkstrom
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.|Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors.forename: Huidong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jagjit
authors.initials: J
authors.lastname: Singh
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Long
authors.affiliation: Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Klein
authors.affiliation: Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Revivicor, Blacksburg, VA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Phelps
authors.affiliation: Revivicor, Blacksburg, VA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Humar
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015478:Antigens, Heterophile / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D055786:Gene Knockout Techniques; D005818:Genetic Engineering; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D010215:Papio; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000379:methods*
chemical_list: D015478:Antigens, Heterophile; D007166:Immunosuppressive Agents; D003165:Complement System Proteins; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine
keywords: anti-IL-6R antagonist; costimulation blockade; genetically engineered; kidney; pig; xenotransplantation