Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging

Thomas Agius, Julien Songeon, Antoine Klauser, Florent Allagnat, Grégoire Longchamp, Raphael Ruttimann, Arnaud Lyon, Julijana Ivaniesevic, Raphael Meier, Sébastien Déglise, James F. Markmann, Korkut Uygun, Leo Buhler, Christian Toso, Jean Marc Corpataux, Francois Lazeyras, Alban Longchamp

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Background. The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods. To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results. Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions. Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.

Original languageEnglish (US)
Pages (from-to)E1354
JournalTransplantation Direct
Issue number10
StatePublished - Sep 26 2022

Bibliographical note

Funding Information:
This work was supported by the Swiss National Science Foundation to J.-M.C., F.L. (SNSF 320030_182658), and A.L. (SNSF PZ00P3-185927), as well as the Mendez National Institute of Transplantation and the Leenards Foundation to AL.

Publisher Copyright:
© 2022 Wolters Kluwer Health. All rights reserved.

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