Hypothermic Oxygenated Perfusion (HOPE) - A simple and effective method to modulate the immune response in kidney transplantation

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 DCD 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 to untreated allogeneic controls. Similarly, HOPE treatment protected recipients of extended DCD kidneys from immune activation. This effect was lost when de-oxygenated 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. Financial Support: None * PK and AS contributed equally as first authors Disclosure statement: The authors declare that they have nothing to disclose. The interpretation and reporting of the here included data are the responsibility of the authors. Correspondence: Philipp Dutkowski, MD, Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Phone: +41 44 255 4236, Fax: +41 44 255 4999, E-mail: philipp.dutkowski@usz.ch Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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