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Hypothermic Oxygenated Perfusion

A Simple and Effective Method to Modulate the Immune Response in Kidney Transplantation

Kron, Philipp1,2; Schlegel, Andrea1,3; Muller, Xavier1; Gaspert, Ariana4; Clavien, Pierre-Alain1; Dutkowski, Philipp, MD1

doi: 10.1097/TP.0000000000002634
Original Basic Science—General
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Background. Hypothermic oxygenated perfusion (HOPE) has been shown to protect liver recipients from acute rejection in an allogeneic model of liver transplantation in rats. Here we investigate the impact of HOPE on the T cell–mediated immune response following kidney transplantation.

Methods. Kidneys from Lewis rats were transplanted into Brown Norway recipients to trigger acute rejection (allogeneic untreated group). Next, Brown Norway recipients were treated either with tacrolimus,= or donor kidneys underwent 1h-HOPE-treatment before implantation without additional immunosuppression in recipients. Syngeneic kidney transplants (Brown Norway to Brown Norway) served as controls. In a second set of experiments, the immune response was assessed in a donation after circulatory death model of kidney transplantation comparing standard cold storage with subsequent HOPE treatment and hypothermic nitrogenated perfusion, where oxygen was replaced during cold perfusion.

Results. Allogeneic kidney transplantation led to death in all untreated recipients within 10 days due to severe acute rejection. In contrast, immune activation was prevented by tacrolimus with significantly improved recipient survival. Similarly, HOPE treatment, without any immunosuppression, protected recipients from acute immune response, as measured by less cytokine release, T-cell, and macrophage activation. Additionally, HOPE-treated kidneys showed better function and less early fibrosis leading to a significantly improved recipient survival, compared with untreated allogeneic controls. Similarly, HOPE treatment protected recipients of extended donation after circulatory death kidneys from immune activation. This effect was lost when deoxygenated perfusate was used.

Conclusions. In summary, this is the first study demonstrating the beneficial effects of HOPE on the immune response following kidney transplantation in an allogeneic rodent model.

1 Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zürich, Switzerland.

2 HPB and Transplant Unit, St James’s University Hospital, Leeds, United Kingdom.

3 The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, United Kingdom.

4 Department of Pathology and Molecular Pathology, University Hospital Zurich, Zürich, Switzerland.

Received 25 August 2018. Revision received 8 January 2019.

Accepted 10 January 2019.

P.K. and A.S. contributed equally as first authors.

The authors declare no funding or conflicts of interest.

The interpretation and reporting of the here-included data are the responsibility of the authors.

P.K., A.S., and P.D. participated in research design. P.K., A.S., and X.M. participated in the performance of the research. P.K., A.S., A.G., P.D., and P.-A. wrote the article. No authors contributed new reagents or analytic tools. P.K, A.S., X.M., and A.G. participated in data analysis.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Philipp Dutkowski, MD, Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. (philipp.dutkowski@usz.ch).

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.