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

Abstract

The longest survival of a nonhuman primate with a life-supporting kidney graft to date has been 90 days, though graft survival >30 days has been unusual. A baboon received a kidney graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for two human complement- and three human coagulation- regulatory proteins (though 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 (0.6–1.6mg/dL) until terminally. 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.

Bringing Home The Bacon: Update on The State of Kidney Xenotransplantation

“…Maximum pig kidney graft survival has increased from minutes to months, and occasionally to >1 year (Fig. 1) [19, 20, 22, 23]. These encouraging results have led to consideration of initial clinical trials.…”

New life for pig-to-human transplants

“…The longest life-supporting transplant was published in June 6 , when Cooper's group announced that a kidney transplant from a Revivicor pig with six modified genes supported a baboon for 136 days.…”

Current status of pig liver xenotransplantation

“…generating multi-gene knockout pigs, such as GGTA1/CMAH/β4GalNT2 genes [32] using a CRISPR/Cas9 technology [33], or multi-gene expressing pigs such as human CD46, human CD55, human Thrombomodulin, human CD39 [34] will reduce antibody binding and may correct consumptive coagulopathy. New preclinical studies in GE pigto-nonhuman primate liver xenotransplantation are warranted using newly available GE pigs, such as ASGR1 knockout, β4GalNT2 knockout, and human SIRPα transgenic pigs.…”