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

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).

Keywords: Renal transplantation; Transplant medicine; Transplant surgery.

Figure 1. Participant timeline, delineating the patient’s clinical care while enrolled in the trial (blue panel), the kidney’s temporal course (yellow panel) and the key time points for sample collection (grey inserts). NMP, normothermic machine perfusion; RBC, red blood cell.

Figure 2. Schematic representation of the XVIVO Kidney Assist perfusion circuit with a CytoSorb filter incorporated. The kidney is placed in a sterile organ chamber with a lid. A patch clamp is used to connect the arterial end of the tubing to the renal artery. The renal vein and ureter drain directly into the venous reservoir (urine recirculation). Additional component parts (not shown) include a pressure transducer, an arterial flow sensor, temperature sensors and sampling ports.