低温氧合灌注：调节肾移植中免疫反应的简单有效方法。

Hypothermic Oxygenated Perfusion: A Simple and Effective Method to Modulate the Immune Response in Kidney Transplantation.

机构信息

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

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

出版信息

Transplantation. 2019 May;103(5):e128-e136. doi: 10.1097/TP.0000000000002634.

DOI:10.1097/TP.0000000000002634

PMID:30747849

Abstract

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.

摘要

背景

在大鼠同种异体肝移植模型中，已证明低温氧合灌注（HOPE）可防止肝受者发生急性排斥反应。在此，我们研究了 HOPE 对肾移植后 T 细胞介导的免疫反应的影响。

方法

将来自 Lewis 大鼠的肾脏移植到 Brown Norway 受者体内，以引发急性排斥反应（未治疗的同种异体对照组）。然后，Brown Norway 受者接受他克莫司治疗，或在不进行受体额外免疫抑制的情况下，供肾在植入前进行 1 小时 HOPE 处理。同基因肾移植（Brown Norway 到 Brown Norway）作为对照。在第二个实验中，通过比较标准冷保存与随后的 HOPE 处理和低温氮合灌注，评估了在捐赠后循环死亡模型中的免疫反应，其中在冷灌注期间用氮气替代氧气。

结果

所有未治疗的受者在 10 天内因严重急性排斥反应而死亡。相比之下，免疫激活被他克莫司抑制，受者存活率显著提高。同样，HOPE 处理（无需任何免疫抑制）也可防止急性免疫反应，表现为细胞因子释放、T 细胞和巨噬细胞激活减少。此外，与未治疗的同种异体对照组相比，HOPE 处理的肾脏功能更好，早期纤维化程度更低，因此受者存活率显著提高。同样，HOPE 处理可防止循环死亡后扩展供体肾脏的受者发生免疫激活。当使用脱氧灌流液时，这种作用会丧失。