Comparison of competing ex vivo preservation techniques and investigation of the mechanisms of graft recovery during ex-vivo perfusion in marginal kidney grafts
Final Report Abstract
This work showed that the addition of oxygen during HMP does not reduce preservation injury in all DCD kidney grafts. In our porcine model of 30min DCD, oxygenation during cold preservation did not show any beneficial results on the short term. Moreover, we found that oxygenated HMP followed by end-ischemic NEVKP is as effective as continuous NEVKP and superior to oxygenated HMP alone. This combination is a practical alternative for a clinical setting, because oxygenated HMP could be easily performed during transportation, while end-ischemic NEVKP can be done back-to-base for graft assessment and treatment. We also found that SEVKP is associated with reduced metabolic activity during perfusion, but results in similar graft function post porcine DCD kidney transplantation compared to NEVKP. Finally, in a pilot clinical trial, we could demonstrate that kidney function after transplantation in grafts which received end-ischemic NEVKP is not inferior to the standard of care, demonstrating the safety and feasibility of NEVKP in a clinical setting. The importance of the clinical study that we performed lies on its immense potential to increase the donor pool. At the moment, grafts are accepted solely based on donor criteria. Implementing NEVKP on a large scale not only has the potential to improve graft preservation and injury, but also offers a platform for graft assessment and treatment. Clinical experience with NEVKP will allow us to develop scores to evaluate kidney graft performance on pump and enable us to design criteria for graft assessment that will objectively correlate with graft function after transplantation.
Publications
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(2020, May). Normothermic Ex Vivo Kidney Perfusion Improves Early DCD Graft Function Compared With Hypothermic Machine Perfusion and Static Cold Storage. Transplantation, 104(5), 947-955
Urbanellis P, Hamar M, Kaths JM, Kollmann D, Linares I, Mazilescu L, Ganesh S., Wiebe A., Yip PM, John R, Konvalinka A, Mucsi I, Ghanekar A, Bagli DJ, Robinson LA, & Selzner M
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Normothermic Ex Vivo Kidney Perfusion for Human Kidney Transplantation: First North American Results. Transplantation. March 2021
Mazilescu LI, Urbanellis P, Kim SJ, et al.
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Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts. Transplant Direct. 2021;7(10):e751
Mazilescu LI, Urbanellis P, Kaths MJ, Ganesh S, Goto T, Noguchi Y, et al.
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Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts. Sci Rep. 2021;11(1):17930
Urbanellis P, Mazilescu L, Kollmann D, Linares-Cervantes I, Kaths JM, Ganesh S, et al.
