The Renin Angiotensin System (RAS) After Pig-to-Baboon Kidney Transplantation
1Surgery, University of Alabama at Birmingham, Birmingham, AL, 2Revivicor, Blacksburg, VA, 3Department of Physiology and Hypertension and Renal Center, Tulane University, New Orleans, LA, 4Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
Meeting: 2022 American Transplant Congress
Abstract number: 79
Keywords: Kidney, Pig, Primates, Renal function
Topic: Basic Science » Basic Science » 13 - Xenotransplantation
Session Information
Session Time: 3:30pm-5:00pm
Presentation Time: 3:50pm-4:00pm
Location: Hynes Room 302
*Purpose: Relatively long-term survival after life-supporting pig-to-baboon kidney transplantation has been achieved. However, there are documented episodes of hypovolemia during the post-transplant period from an unknown mechanism. There is some evidence in the literature that pig renin does not cleave primate angiotensinogen which would suggest that the RAS pathway may be compromised post-kidney xenotransplantation.
*Methods: Kidneys were harvested from pigs with several genetic modifications and were transplanted into 5 immunosuppressed baboons after excision of the native kidneys. Induction immunosuppressive therapy consisted of thymoglobulin, anti-CD20mAb, cobra venom factor or C-1 esterase inhibitor, and maintenance therapy consisted of anti-CD40mAb, rapamycin, and low-dose corticosteroids. Plasma renin, angiotensinogen, and angiotensin II levels, and urine osmolality and electrolytes were measured in (i) healthy, genetically-modified pigs (n=2), healthy non-immunosuppressed baboons (n=4), and (iii) baboons with life-supporting pig kidney grafts (n=5).
*Results: Plasma renin levels were not significantly different between healthy pigs, healthy baboons, and baboons with pig kidney grafts indicating that the grafts are able to release renin into the circulation. Plasma angiotensin II levels trended lower from pre-transplant levels even though plasma angiotensinogen levels were increased and measured renin was abundant. Urine osmolality and urine sodium concentrations were decreased post-xenotransplantation.
*Conclusions: Lowering of plasma angiotensin II levels in baboons with pig kidney grafts even in the presence of increasing angiotensinogen may be due to reduced reactivity of pig renin to cleave baboon angiotensinogen, suggesting a reduced capacity to elicit a robust response of the RAS to hypovolemic and hypotensive episodes. The reduced urine osmolality and sodium concentration reflects the decreased ability of the pig kidney to concentrate urine. However, these considerations should not prohibit successful clinical application of pig kidney xenotransplantation.
To cite this abstract in AMA style:
Hansen-Estruch C, Bikhet MH, Javed M, Ayares D, Katsurada A, Satou R, Shao W, Cooper DK, Navar LG, Judd E. The Renin Angiotensin System (RAS) After Pig-to-Baboon Kidney Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/the-renin-angiotensin-system-ras-after-pig-to-baboon-kidney-transplantation/. Accessed May 18, 2025.« Back to 2022 American Transplant Congress