Joint first authors
Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date
Version of Record online: 29 JUN 2015
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Volume 22, Issue 4, pages 302–309, July/August 2015
How to Cite
Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date. Xenotransplantation 2015; 22: 302–309. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., , , , , , , , , , , , , , .
- Issue online: 27 JUL 2015
- Version of Record online: 29 JUN 2015
- Manuscript Accepted: 4 JUN 2015
- Manuscript Received: 2 JUN 2015
- NIH grants. Grant Numbers: #U19 AI090959, #U01 AI068642, # R21 A1074844
- University of Pittsburgh and Revivicor, Inc., Blacksburg, VA
- NIH P40. Grant Number: RR012317-09
- anti-IL-6R antagonist;
- costimulation blockade;
- genetically engineered;
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.