Life-supporting Kidney Xenotransplantation from Genetically Engineered Pigs in Baboons: A Comparison of Two Immunosuppressive Regimens

Takayuki Yamamoto, Hidetaka Hara, Jeremy Foote, Liaoran Wang, Qi Li, Edwin C. Klein, Hendrik Jan Schuurman, Hongmin Zhou, Juan Li, A. Joseph Tector, Zhongqiang Zhang, Mohamed Ezzelarab, Ray Lovingood, David Ayares, Devin E. Eckhoff, David K.C. Cooper, Hayato Iwase

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background. The aims of this study were to evaluate the efficacy of US Food and Drug Administration-approved drugs in genetically engineered pig-to-baboon kidney xenotransplantation and compare the results with those using an anti-CD40 monoclonal antibody (mAb)-based regimen. Methods. Ten life-supporting kidney transplants were carried out in baboons using α1,3-galactosyltransferase gene-knockout/CD46 pigs with various other genetic manipulations aimed at controlling coagulation dysregulation. Eight transplants resulted in informative data. Immunosuppressive therapy consisted of induction with antithymocyte globulin and anti-CD20mAb, and maintenance based on either (1) CTLA4-Ig and/or tacrolimus (+rapamycin or mycophenolate mofetil) (GroupA [US Food and Drug Administration-approved regimens], n = 4) or (2) anti-CD40mAb + rapamycin (GroupB, n = 4). All baboons received corticosteroids, interleukin-6R blockade, and tumor necrosis factor-α blockade. Baboons were followed by clinical and laboratory monitoring of kidney function, coagulation, and immune parameters. At euthanasia, morphological and immunohistochemical studies were performed on the kidney grafts. Results. The median survival in GroupB was 186 days (range 90-260), which was significantly longer than in GroupA; median 14 days (range 12-32) (P < 0.01). Only GroupA baboons developed consumptive coagulopathy and the histopathological features of thrombotic microangiopathic glomerulopathy and interstitial arterial vasculitis. Conclusions. Recognizing that the pig donors in each group differed in some genetic modifications, these data indicate that maintenance immunosuppression including anti-CD40mAb may be important to prevent pig kidney graft failure.

Original languageEnglish (US)
Pages (from-to)2090-2104
Number of pages15
JournalTransplantation
Volume103
Issue number10
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

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