一项单中心随机试验研究方案，旨在评估在肾脏常温机器灌注期间添加CytoSorb过滤器以在肾移植前去除炎症和免疫介质的安全性和可行性。

Protocol for a single-centre randomised pilot study to assess the safety and feasibility of adding a CytoSorb filter during kidney normothermic machine perfusion to remove inflammatory and immune mediators prior to kidney transplantation.

作者信息

Mehta Maithili, Hosgood Sarah, Nicholson Michael L

机构信息

Department of Surgery, University of Cambridge, Cambridge, UK.

Department of Surgery, University of Cambridge, Cambridge, UK

出版信息

BMJ Open. 2025 Mar 29;15(3):e093001. doi: 10.1136/bmjopen-2024-093001.

DOI:10.1136/bmjopen-2024-093001

PMID:40157734

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11956346/

Abstract

INTRODUCTION

The introduction of perfusion technologies in kidney transplantation has the potential to improve graft function and survival and increase utilisation. Our previous work demonstrated that kidneys with an enhanced inflammatory and immune response during normothermic machine perfusion (NMP) had significant graft dysfunction after transplantation. The addition of a cytokine filter (CytoSorb) to the NMP circuit dramatically reduces both circulating inflammatory mediators and inflammatory gene expression, but this has not been trialled in clinical practice.

METHODS AND ANALYSIS

This is a randomised phase 1 pilot study to evaluate the safety and feasibility of using a CytoSorb filter in clinical NMP to remove inflammatory and immune mediators. Eligible kidney transplant recipients on the waiting list in the East of England will be approached for consent. A total of 20 patients will be recruited and randomised in a 1:1 ratio for the donor kidney to receive either NMP or NMP with a CytoSorb filter pre-transplantation. The kidney will be transplanted according to standard practice after NMP. The primary endpoint is inflammatory and immune gene expression measured in a cortical biopsy from the kidney 60 min post-transplant. Secondary endpoints include rates and duration of delayed graft function and graft function as assessed by change in creatinine clearance and estimated glomerular filtration rate 2 days, 5 days, 1 month and 3 months post-transplant. Additionally, inflammatory mediators and injury markers will be measured in peripheral blood and urine samples taken pre-operatively and on days 2 and 5 after transplant.

ETHICS AND DISSEMINATION

This study has been approved by the Health Research Authority Health and Care Research Wales Committee (REC 23/WM/0141) and by National Health Service (NHS) Blood and Transplant (Ref: Study 148). Findings will be published in a peer-reviewed journal and disseminated at scientific conferences. The dataset will be made available on request.

TRIAL REGISTRATION

The study is prospectively registered on the ISCRTN registry (ID: 13698207).

摘要

引言

肾脏移植中灌注技术的引入有可能改善移植物功能和存活率，并提高利用率。我们之前的研究表明，在常温机器灌注（NMP）期间炎症和免疫反应增强的肾脏在移植后会出现明显的移植物功能障碍。在NMP回路中添加细胞因子过滤器（CytoSorb）可显著降低循环中的炎症介质和炎症基因表达，但这尚未在临床实践中进行试验。

方法与分析

这是一项随机1期试点研究，旨在评估在临床NMP中使用CytoSorb过滤器去除炎症和免疫介质的安全性和可行性。将联系英格兰东部等待名单上符合条件的肾移植受者征求同意。总共将招募20名患者，并按1:1的比例随机分配供体肾脏，使其在移植前接受NMP或带有CytoSorb过滤器的NMP。在NMP后，肾脏将按照标准做法进行移植。主要终点是移植后60分钟从肾脏获取的皮质活检中测量的炎症和免疫基因表达。次要终点包括移植后2天、5天、1个月和3个月时通过肌酐清除率变化和估计肾小球滤过率评估的延迟移植物功能的发生率和持续时间以及移植物功能。此外，将在术前以及移植后第2天和第5天采集的外周血和尿液样本中测量炎症介质和损伤标志物。