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

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

doi:10.1097/TXD.0000000000001354

Transplantation Direct (Oct 2022)

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

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

Affiliations

Thomas Agius, MS: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.
Julien Songeon, MS: 2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.
Antoine Klauser, PhD: 2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.
Florent Allagnat, PhD: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.
Grégoire Longchamp, MD: 4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
Raphael Ruttimann, BS: 4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
Arnaud Lyon, MD: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.
Julijana Ivaniesevic, PhD: 5 Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Switzerland.
Raphael Meier, MD, PhD: 6 Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Sébastien Déglise, MD: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.
James F. Markmann, MD, PhD: 7 Department of Surgery, Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Korkut Uygun, PhD: 8 Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Leo Buhler, MD: 9 Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Fribourg, Switzerland.
Christian Toso, MD, PhD: 4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
Jean-Marc Corpataux, MD: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.
Francois Lazeyras, PhD: 2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.
Alban Longchamp, MD, PhD: 1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.

DOI: https://doi.org/10.1097/TXD.0000000000001354
Journal volume & issue: Vol. 8, no. 10
p. e1354

Abstract

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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.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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