Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts From Brain Death Donors

Study Overview
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Brief Summary
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Kidney transplantation (KT) has emerged as the mainstay of treatment for end-stage kidney disease. In an effort to address the widening gap between demand and supply of donor organs, there has been an increase in the numbers of marginal or functionally impaired renal allografts that had to be accepted for KT over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function (PNF) and/or delayed graft function (DGF). Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in pre-clinical experiments and in a few clinical series of donation after cardiac death (DCD) in liver transplantation. The present trial is an investigator-initiated pilot study on the effects of HOPE on ECD-allografts in donation after brain death (DBD) KT. Fifteen kidney allografts will be submitted to 2 hours of HOPE before implantation and are going to be compared to a case matched group transplanted after conventional cold storage (CCS).

Detailed Description
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The present trial is an investigator-initiated pilot study on the effects of HOPE on ECD-allografts in DBD KT. Fifteen kidney allografts with defined inclusion/exclusion criteria will be submitted to 2 hours of HOPE via the renal artery before implantation and are going to be compared to a case matched group of 30 patients (1:2 matching) transplanted after CCS. Besides the clinical evaluation of HOPE-reconditioned allograft function, a targeted biomarker analysis is planned using tissue, serum, and urine samples as the translational and basic research aspect of the present study.

Official Title
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Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts From Brain Death Donors - a Prospective Cohort Study

Conditions
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Reperfusion Injury, Hypothermic Oxygenated Machine Perfusion

Intervention / Treatment
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* Procedure: HOPE
* Other: Conventional cold storage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dialysis-requiring Patients, suffering from end stage kidney disease, listed for KT and receiving ECD organs at the Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany. Informed consent is obtained from all subjects participating in the trial by a qualified member of the study team. ECD is defined as followed: deceased donors > 60 years and older, and those aged between 50-59 years with at least two of the following conditions: cerebrovascular cause of death, serum Creatinine greater than 1.5 mg/dL (132.6 µmol/L), history of arterial hypertension Exclusion Criteria: Recipients of living donor kidney transplants Previous kidney transplantation Participation in other kidney related trials The subject received an investigational drug within 30 days prior to inclusion The subject is unwilling or unable to follow the procedures outlined in the protocol The subject is mentally or legally incapacitated Non-German or non-English speakers Family members of the investigators or employees of the participating department The subject is mentally or legally incapacitated The subject suffers from uncontrolled bacterial or viral infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot study, case matched (1:2)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional cold storage<br>Conventional static cold storage (CCS) on temperature 0-4 °C from organ procurement (historical case matched group) | Other: Conventional cold storage<br>* No intervention<br>|
| Experimental: Hypothermic oxygenated perfusion (HOPE)<br>HOPE for 1 hour via the renal artery in a recirculating and pressure controlled system, Belzer (UW) machine perfusion solution, perfusate temperature 0-4 °C, perfusate oxygenation pO2 of 60-80 kPa Other Name: Hypothermic machine perfusion (HMP) | Procedure: HOPE<br>* HOPE for 1 hour via the renal artery in a recirculating and pressure controlled system, Belzer (UW) machine perfusion solution, perfusate temperature 0-4 °C, perfusate oxygenation pO2 of 60-80 kPa Other Name: Hypothermic machine perfusion (HMP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DGF | DGF (defined as the need for dialysis in the first 7-days post-transplantation) | 7 days post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRR2, CRR5 | Creatinine reduction ratio day 2 (CRR2= creatinine day 1-creatinine day 2/creatinine day 1) and CRR5 (CRR5=pre-transplant creatinine-creatinine day 5/pre-transplant creatinine) | 5 days post-transplant | 
| postoperative complications | Clavien-Dindo complication score | Subjects will be followed 6 months postoperatively | 
| Cumulative postoperative complications | Comprehensive complication index (CCI) | Subjects will be followed 6 months postoperatively | 
| Duration of intensive care stay | Duration of ICU stay | Subjects will be followed 6 months postoperatively | 
| Duration of hospital stay | Duration of hospitalisation | Subjects will be followed 6 months postoperatively | 
| Graft survival | Six months graft survival | Subjects will be followed 6 months postoperatively | 
| Renal function | Renal function (serum creatinine and estimated glomerular filtration rate (eGFR)) | Subjects will be followed 6 months postoperatively | 
| Perfusion Parameter | Flow and thus renal resistance | During HOPE | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HOPE, Extended criteria donor, Donation after brain death, Kidney transplantation