Additional Normothermic Machine Perfusion Versus Hypothermic Machine Perfusion in Suboptimal Donor Kidney Transplantation: Protocol of a Randomized, Controlled, Open-Label Trial

Abstract

Introduction: Ageing of the general population has led to an increase in the use of suboptimal kidneys from expanded criteria donation after brain death (ECD-DBD) and donation after circulatory death (DCD) donors. However, these kidneys have inferior graft outcomes and lower rates of immediate function. Normothermic machine perfusion (NMP) may improve outcomes of these suboptimal donor kidneys. Previous nonrandomized studies have shown the safety of this technique and suggested its efficacy in improving the proportion of immediate functioning kidneys compared to static cold storage (SCS). However, its additional value to hypothermic machine perfusion (HMP), which has already been proved superior to SCS, has not yet been established. Methods and analysis:This single-center, open-label, randomized controlled trial aims to assess immediate kidney function after 120 minutes additional, end-ischemic NMP compared to HMP alone. Immediate kidney function is defined as no dialysis treatment in the first week after transplant. Eighty recipients on dialysis at the time of transplant who receive an ECD-DBD or DCD kidney graft are eligible for inclusion. In the NMP group, the donor kidney is taken of HMP upon arrival in the recipient hospital and thereafter put on NMP for 120 minutes at 37 degrees Celsius followed by transplantation. In the control group, donor kidneys stay on HMP until transplantation. The primary outcome is immediate kidney function. Ethics and dissemination:The protocol has been approved by the Medical Ethical Committee of Erasmus Medical Center (2020-0366). Results of this study will be submitted to peer-reviewed journals.Registration: registered in clinicaltrials.gov (NCT04882254). Highlights:• This is the first RCT to compare additional NMP to HMP alone.• Extensive sampling will offer in-depth analysis of kidney physiology during NMP.• This RCT may help identify biomarkers to predict clinical outcomes during NMP.• Biomarkers can help develop NMP as assessment tool for declined kidneys.

Taurine as Antioxidant in a Novel Cell- and Oxygen Carrier-Free Perfusate for Normothermic Machine Perfusion of Porcine Kidneys

“…NMP also offers the possibility of viability assessment and pharmaceutical intervention prior to transplantation, in contrast to static cold storage (SCS) or hypothermic machine perfusion (HMP) [ 7 , 8 ]. As shown previously in cohort studies, NMP is capable of reducing PNF and DGF and improving immediate kidney function [ 9 , 10 , 11 , 12 , 13 ].…”

Tissue-resident Lymphocytes Are Released During Hypothermic and Normothermic Machine Perfusion of Human Donor Kidneys

“…This ancillary study involved the prospective collection of kidney perfusates obtained during HMP and NMP of donor kidneys enrolled in the APOLLO clinical trial (NCT04882254). 16 The sample collection took place at the Erasmus MC Transplant Institute, University Medical Center, Rotterdam, the Netherlands, from April 2021 to July 2023. Donor kidneys that were from donation after circulatory death (DCD) donors or donation after brain death (DBD) donors fulfilling the expanded criteria donor criteria were included in the APOLLO trial.…”

“…Additionally, kidneys in the trial’s intervention arm underwent a supplementary 120-min NMP cycle ( Figure S1, SDC , http://links.lww.com/TP/C970 ). 16 The NMP perfusate primarily consisted of leukocyte-depleted packed red blood cells (RBCs), matched to the recipient’s blood type. 16 HMP samples originated from either the trial’s control arm or from routine kidney transplantations.…”

Human Transplant Kidneys on Normothermic Machine Perfusion Display Endocrine Activity

“…For the NMP intervention group, 15 donor kidneys underwent 2 h additional, end-ischemic NMP with a plasma-free red cell–based solution before transplantation upon arrival at the Erasmus Medical Center. The perfusate composition of NMP in this study is listed in Table S1 ( SDC, http://links.lww.com/TXD/A542 ) and the perfusate did not contain 25(OH)D. 21 Perfusate samples were collected at time point 0, 1, and 2 h NMP, followed by the removal of red blood cells with a 2-μm filter (Whatman). Then the perfusate was snap-frozen and stored at –80 °C for the measurements of prorenin/renin, EPO, and vitamin D levels.…”