Hypothermic Oxygenated Machine Perfusion, Reperfusion Injury
Conditions
Keywords
Extended criteria donor, Donation after brain death, HOPE, Kidney transplantation
Brief summary
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
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.
Interventions
PROCEDUREHOPE
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)
No intervention
Sponsors
University Hospital, Aachen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pilot study, case matched (1:2)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
1. Recipients of living donor kidney transplants 2. Previous kidney transplantation 3. Participation in other kidney related trials 4. The subject received an investigational drug within 30 days prior to inclusion 5. The subject is unwilling or unable to follow the procedures outlined in the protocol 6. The subject is mentally or legally incapacitated 7. Non-German or non-English speakers 8. Family members of the investigators or employees of the participating department 9. The subject is mentally or legally incapacitated 10. The subject suffers from uncontrolled bacterial or viral infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DGF | 7 days post-transplant | DGF (defined as the need for dialysis in the first 7-days post-transplantation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| postoperative complications | Subjects will be followed 6 months postoperatively | Clavien-Dindo complication score |
| Cumulative postoperative complications | Subjects will be followed 6 months postoperatively | Comprehensive complication index (CCI) |
| Duration of intensive care stay | Subjects will be followed 6 months postoperatively | Duration of ICU stay |
| CRR2, CRR5 | 5 days post-transplant | 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) |
| Graft survival | Subjects will be followed 6 months postoperatively | Six months graft survival |
| Renal function | Subjects will be followed 6 months postoperatively | Renal function (serum creatinine and estimated glomerular filtration rate (eGFR)) |
| Perfusion Parameter | During HOPE | Flow and thus renal resistance |
| Duration of hospital stay | Subjects will be followed 6 months postoperatively | Duration of hospitalisation |
Countries
Germany
Outcome results
None listed