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The future of marginal kidney repair in the context of normothermic machine perfusion.

ABSTRACT: Normothermic machine perfusion (NMP) is a technique that utilizes extracorporeal membrane oxygenation to recondition and repair kidneys at near body temperature prior to transplantation. The application of this new technology has been fueled by a significant increase in the use of the kidneys that were donated after cardiac death, which are more susceptible to ischemic injury. Preliminary results indicate that NMP itself may be able to repair marginal organs prior to transplantation. In addition, NMP serves as a platform for delivery of therapeutics. The isolated setting of NMP obviates problems of targeting a particular therapy to an intended organ and has the potential to reduce the harmful effects of systemic drug delivery. There are a number of emerging therapies that have shown promise in this platform. Nutrients, therapeutic gases, mesenchymal stromal cells, gene therapies, and nanoparticles, a newly explored modality, have been successfully delivered during NMP. These technologies may be effective at blocking multiple mechanisms of ischemia- reperfusion injury (IRI) and improving renal transplant outcomes. This review addresses the mechanisms of renal IRI, examines the potential for NMP as a platform for pretransplant allograft modulation, and discusses the introduction of various therapies in this setting.

SUBMITTER: DiRito JR

PROVIDER: S-EPMC6175453 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The future of marginal kidney repair in the context of normothermic machine perfusion.

DiRito Jenna R JR Hosgood Sarah A SA Tietjen Gregory T GT Nicholson Michael L ML

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20180702 10

Normothermic machine perfusion (NMP) is a technique that utilizes extracorporeal membrane oxygenation to recondition and repair kidneys at near body temperature prior to transplantation. The application of this new technology has been fueled by a significant increase in the use of the kidneys that were donated after cardiac death, which are more susceptible to ischemic injury. Preliminary results indicate that NMP itself may be able to repair marginal organs prior to transplantation. In addition ...[more]

PMID: 29878499

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Project description:A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2-10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5-037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.

Project description: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 non-randomized 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.

Dataset Information

The future of marginal kidney repair in the context of normothermic machine perfusion.

Publications

The future of marginal kidney repair in the context of normothermic machine perfusion.

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