Initial Experience with Growth Hormone Receptor Knockout in Pig-to-Baboon Kidney Transplantation: Effect on Ureteric Viability and Kidney Growth

C. Hansen-Estruch¹, H. Iwase¹, A. Jagdale¹, T. Yamamoto¹, M. H. Bikhet¹, J. Foote², H. Hara¹, D. Anderson¹, P. Porrett¹, D. Eckhoff¹, D. Ayares³, W. Eyestone³, J. Locke¹, D. K. Cooper¹

¹Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, ²Department of Microbiology and Animal Resources Program, University of Alabama at Birmingham, Birmingham, AL, ³Revivicor, Blacksburg, VA

Meeting: 2021 American Transplant Congress

Abstract number: 590

Keywords: Anastomatic healing, Kidney transplantation, Pig, Primates

Topic: Basic Science » Xenotransplantation

Session Information

Session Name: Xenotransplantation

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: The purpose of this study was to report outcomes of pig-to-baboon renal transplants using a novel growth hormone receptor knockout (GHRKO) organ-source pig created to address rapid initial kidney graft growth seen in prior xenotransplant experiments.

*Methods: Kidney transplants from pigs expressing the GHRKO modification were carried out in 13 baboons. The immunosuppressive regimen included induction therapy with ATG (Thymoglobulin), anti-CD20mAb (Rituximab), and cobra venom factor or a C1-esterase inhibitor, and maintenance therapy based on anti-CD40mAb, rapamycin, and low-dose steroids. In Group A (n=7), a standard surgical procedure was carried out, as previously described, including bilateral native nephrectomy and graft implantation to the aorta and inferior vena cava. In Group B (n=6), much greater peri-ureteral tissue was maintained with the graft.

*Results: Five of the first 7 baboons (71%) (Group A) developed a urinary leak between 8 and 25 days post-transplant from necrosis of the distal pig ureter, a complication we have never seen previously. In one case, the entire ureter had necrosed. In 2 of the 5 cases, histopathological features of antibody-mediated rejection were present in the kidney and ureter. In Group B, modifications to the surgical technique to ensure retention of vascularity of the ureter, e.g., maintenance of peri-ureteric tissue, prevented a ureteric leak. Baboons from both groups with graft survival greater than 30 days demonstrated an approximate 40% reduced graft growth compared with historic controls as measured by kidney dimensions seen on ultrasound.

*Conclusions: Grafts from GHRKO pigs have reduced growth post-transplant compared to historical controls. GHRKO may have a detrimental effect on healing of the anastomosis between the graft ureter and recipient bladder, but does not affect healing of the vascular anastomoses or the abdominal wound. Taking special steps to maintain ureteric vascularity can prevent this problem.

To cite this abstract in AMA style:

Hansen-Estruch C, Iwase H, Jagdale A, Yamamoto T, Bikhet MH, Foote J, Hara H, Anderson D, Porrett P, Eckhoff D, Ayares D, Eyestone W, Locke J, Cooper DK. Initial Experience with Growth Hormone Receptor Knockout in Pig-to-Baboon Kidney Transplantation: Effect on Ureteric Viability and Kidney Growth [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/initial-experience-with-growth-hormone-receptor-knockout-in-pig-to-baboon-kidney-transplantation-effect-on-ureteric-viability-and-kidney-growth/. Accessed November 21, 2024.

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