Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo

Rabindra N. Bhattacharjee; Aushanth Ruthirakanthan; Qizhi Sun; Mahms Richard-Mohamed; Sean Luke; Larry Jiang; Shahid Aquil; Hemant Sharma; Mauro E. Tun-Abraham; Bijad Alharbi; Aaron Haig; Alp Sener; Patrick P.W. Luke

Kidney International Reports (Sep 2019)

Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo

Rabindra N. Bhattacharjee,
Aushanth Ruthirakanthan,
Qizhi Sun,
Mahms Richard-Mohamed,
Sean Luke,
Larry Jiang,
Shahid Aquil,
Hemant Sharma,
Mauro E. Tun-Abraham,
Bijad Alharbi,
Aaron Haig,
Alp Sener,
Patrick P.W. Luke

Affiliations

Rabindra N. Bhattacharjee: Matthew Mailing Centre for Translational Transplantation Studies, London Health Sciences Centre, London, Ontario, Canada; Department of Surgery, London Health Sciences Centre, London, Ontario, Canada; Western University, London Health Sciences Centre, London, Ontario, Canada
Aushanth Ruthirakanthan: Western University, London Health Sciences Centre, London, Ontario, Canada
Qizhi Sun: Matthew Mailing Centre for Translational Transplantation Studies, London Health Sciences Centre, London, Ontario, Canada
Mahms Richard-Mohamed: Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Sean Luke: Western University, London Health Sciences Centre, London, Ontario, Canada
Larry Jiang: Western University, London Health Sciences Centre, London, Ontario, Canada
Shahid Aquil: Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Hemant Sharma: Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Mauro E. Tun-Abraham: Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Bijad Alharbi: Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Aaron Haig: Western University, London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Alp Sener: Department of Surgery, London Health Sciences Centre, London, Ontario, Canada; Western University, London Health Sciences Centre, London, Ontario, Canada; Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Patrick P.W. Luke: Matthew Mailing Centre for Translational Transplantation Studies, London Health Sciences Centre, London, Ontario, Canada; Department of Surgery, London Health Sciences Centre, London, Ontario, Canada; Western University, London Health Sciences Centre, London, Ontario, Canada; Multi Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada; Correspondence: Patrick P.W. Luke, London Health Sciences, 339 Windermere Road, London, Ontario, Canada N6A 5A5.

Journal volume & issue: Vol. 4, no. 9
pp. 1323 – 1333

Abstract

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Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. Methods: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 °C, 22 °C, and 37 °C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 °C. Results: Compared with all other groups, 22 °C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 °C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 °C was the optimal temperature to minimize hemorrhage and blood clots. Conclusion: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions. Keywords: donation after cardiac death, ischemia-reperfusion injury, kidney transplantation, oxygenated perfusion, prolonged storage, subnormothermia

Published in Kidney International Reports

ISSN: 2468-0249 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the genitourinary system. Urology
Website: http://www.journals.elsevier.com/kidney-international-reports/

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