PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration

Study Overview
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Brief Summary
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The investigators would like to introduce and clinically evaluate prolonged normothermic machine perfusion (PNMP) to preserve and assess high-risk donor kidneys prior to transplantation.

Detailed Description
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Currently kidney transplantation is the only viable option for patients with kidney failure to regain quality of life and health. The number of organs available for transplantation is insufficient with a widening gap between supply and demand. Nowadays, centers accept older and higher risk donor organs with co-morbidity, often leading to non-function, complications and with half of the patients back on dialysis within 15 years. Furthermore, many donor kidneys have to be discarded as too damaged and beyond repair. Increasing the quality and therefore transplantability of these high-risk donor organs could significantly increase the donor kidney pool. Using prolonged normothermic perfusion of marginal donor organs, the investigators aim to kick start regeneration in the kidney before transplantation, improving function and survival long-term. Furthermore, the choice to accept or decline a donor kidney organ is currently based on subjective criteria and causes great uncertainty amongst clinicians. There is a dire need for tools to aid in decision making and reduce this uncertainty. Biomarkers predictive of graft regeneration are lacking. Samples from perfused kidneys and donor recipients will be collected and analysed to allow the formulation of a kidney fitness index.

Official Title
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PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Procedure: Prolonged normothermic machine perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing 1st or 2nd kidney transplant Patients undergoing a kidney transplantation from DCD Maastricht III & V Transplant recipients aged ≥ 18 years Written informed consent Exclusion Criteria: Patients undergoing 3rd or subsequent kidney transplant Patients undergoing a kidney transplantation from DCD Maastricht I, II & IV Transplant recipients aged < 18 years Patients receiving multi-organ transplants ABO/HLA incompatible transplants Highly sensitized patients with a panel-reactive antibody (PRA) ≥85% Kidneys with CIT > 12 hrs at the point of arrival at transplant centre Kidneys with complex vascular anatomy (≥3 arteries, artery which cannot be can-nulated or attached to the patch holder) Kidneys explanted from a donor on normothermic regional perfusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged normothermic machina perfusion<br>Eligible and consenting patients who will receive a donor kidney will be included for participation in this study. Current practice is to preserve donor kidneys on hypothermic machine perfusion (HMP). In this study, donor kidneys (n=18) will be taken off the HMP after arrival in the transplant center. These will then be perfused with oxygenated perfusate using the NMP device following an optimised NMP protocol. | Procedure: Prolonged normothermic machine perfusion<br>* First, a cohort of DCD kidneys (n=6) will be subjected to 1 hour of NMP and subsequently transplanted [NMP1]. Before extending the duration, secondary endpoints will be evaluated. Thereafter, the duration of NMP will be prolonged to 3 hours (n=6) [PNMP3] and consequently 6 hours (n=6) [PNMP6].<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glomerular filtration rate (GFR) | renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation | 6 months post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glomerular filtration rate (GFR) | renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation | 1 month post transplantation | 
| glomerular filtration rate (GFR) | renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation | 3 months post transplantation | 
| primary non-function | defined as permanent lack of graft function from the time of transplantation, was diagnosed when a kidney graft was well perfused (confirmed by ultrasound examination) but never functioned, necessitating dialysis after kidney transplantation | 6 months post transplantation | 
| delayed graft function (DGF) | defined as the need for postoperative dialysis during the first 7 days after transplantation | 6 months post transplantation | 
| patient and graft survival | time from transplant to patient death, and graft failure | 6 months post transplantation | 
| adverse events | defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the normothermic machine perfusion of the donor kidney prior to transplantation | 6 months post transplantation | 
| postoperative complications | graded according to the comprehensive complication index | 6 months post transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplantation, normothermic machine perfusion, kidney transplantation