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Organ preservation and perfusion

Wednesday September 25, 2024 - 13:40 to 15:10

Room: Çamlıca

448.3 Benefit of hypothermic perfusion on kidney graft survival while adding cold ischemia time

John J. J Fung, United States

Director, UCM Transplant Institute
Surgery
University of Chicago

Biography

John J. Fung, M.D., Ph.D. is the Director of the UChicago Medicine Transplantation Institute. Prior to that, he served as Chairman of the Cleveland Clinic Health System Center for Transplantation, as well as the former Chief of the Division of Transplant Surgery at the University of Pittsburgh. With over 30 years of involvement in abdominal and cellular transplantation, he is also an accomplished immunologist. Dr. Fung received his B.A. from the Johns Hopkins University in 1975, followed by a Ph.D. in Immunology in 1980 and M.D. in 1982 from the University of Chicago. He completed his surgical residency at the University of Rochester, and a transplant surgery fellowship at the University of Pittsburgh, under the guidance of Dr. Thomas Starzl. Between 1987 and 1988, he served as Director of Histocompatibility Testing at the University of Rochester. In 1989, he joined the faculty at the University of Pittsburgh and held the tenured position as the inaugural Thomas E. Starzl Professor in Surgery. He joined the Cleveland Clinic in 2004 as the Chairman of the Department of General Surgery and Professor of Surgery at the Lerner College of Medicine at Case Western University. He also served as the Medical Director of Allogen Laboratory, one of the largest histocompatibility laboratories in the United States and oversaw transplantation services at five Cleveland Clinic facilities globally. In 2016, he was recruited to serve as the Director of the newly created University of Chicago Medicine Transplantation Institute. Dr. Fung is a member of numerous scientific and surgical societies and served as President of the International Liver Transplantation Society from 1997-1999. He is currently Secretary of the Transplantation Society. He has published over 1,000 articles and book chapters and serves on the editorial board for several medical journals. He is the immediate past Editor-in-Chief for Liver Transplantation, the highest impact factor specialty transplant journal. His principal research interests are in transplantation immunology, immunosuppressive therapies, and liver related immunology. In addition, he has received numerous prestigious lay and professional awards. His research interests are in transplant immunology, liver immunity, immnosuppression, and outcomes analysis. Dr. Fung is active in community affairs and is presently the President of The Transplantation Society. He received an honorable discharge from the United States Army Reserve Medical Corps with the rank of Lieutenant Colonel. He and his wife, Beth have four children: Justin, Lauren, Brendan and Shannon

Abstract

Benefit of hypothermic perfusion on kidney graft survival while adding cold ischemia time

Angelica Perez-Gutierrez1, Rita McGill2, Jessica Cao1, Piotr Bachul1, Rolf N Barth1, John Fung1.

1Surgery, University of Chicago , Chicago, IL, United States; 2Medicine, University of Chicago , Chicago, IL, United States

Introduction: Extended cold ischemia time is associated with higher incidence of delayed graft function, primary non-function, and graft failure (1).
Kidneys on hypothermic perfusion have better performance than similar kidneys on ice (2), however the benefit of pumping a kidney and adding cold ischemia time versus ice storage with less cold ischemia time remains unclear, as does the question of how long is safe to wait. 
Understanding the safety implications of using kidneys with prolonged cold ischemia time is crucial. Especially considering logistical factors, such as the additional time needed for crossmatch; recipient challenges that require selecting a different recipient (Ej. COVID-19), or the preference for performing complicated surgeries during regular daytime hours when more resources are available.
Methods: This is an analysis of deceased kidney transplants performed from 2005 to 2022 from the UNOS database. We excluded multi-organ, re-transplant, en-bloc, pediatric transplants, and patients who received alternative immunosuppression. 
A multivariable Cox model for death-censored graft failure was constructed with 145,623 deceased donor kidney transplants, using kidneys with 11-13 hours on ice as a reference. The model was adjusted for recipient, donor and transplant characteristics shown in Table 1.
Results: A total of 145,623 transplant cases were analyzed. The median cold ischemia time was 18 +/- 9 hrs. 30.9% of the cases were pumped and sent on pump, 51.8% were stored on ice, and 17.3% were pumped and sent on ice. The median of graft survival follow up was 3.9 years (min 1.6, max 7). Table 1 shows the distribution of the recipient, donor and transplant characterisitcs by surival outcome. 

Kidneys on hypothermic perfusion have better graft survival than their contra parts on ice with the same CIT. Kidneys with 24 to 36 hours of CIT showed similar censored death graft survival than a reference kidney on ice for ~ 12 hours (HR 1 95% CI 0.93,1.07). Figure 1 shows the hazard ratio of death censored graft failure for kidneys on ice or pump compared to a reference kidney on ~12 hours on ice. 

Kidneys with CIT > 36 hours have higher incidence of death censored graft failure regardless of the storage method.
Conclusions: Hypothermic perfusion is an effective strategy for mitigating the effects of prolonged CIT, thus providing greater flexibility in donor and recipient logistics. Prolonged CIT on pump, up to 36 hours has equivalent graft survival than kidneys with less than 12 hours on ice. 

References
1. Lum EL, Homkrailas P, Abdalla B, et al.  Cold Ischemia Time, Kidney Donor Profile Index, and Kidney Transplant Outcomes: A Cohort Study. Kidney Med. 2022;5(1).
2. Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19.

References:

[1] cold ischemia time
[2] hypothermic perfusion
[3] kidney transplant

Presentations by John J. J Fung

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