Limitation of Ischemic Injury of a Kidney Stored in Machine Perfusion in Hypothermia - Evaluation of the Impact on Kidney Allograft Function

Study Overview
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Brief Summary
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The aims of this study are: assessment of ischemia injury of kidney retrieved from standard and expanded criteria deceased donor before transplantation assessment of efficacy of kidney ischemia injury decreasing assessment of influence of kidney ischemia injury decreasing on its function after transplantation For the purpose of this research one hundred kidney will be retrieved from deceased donors (standard and expanded criteria deceased donors) for transplantation. All kidneys before transplantation will be stored in machine perfusion in hypothermia with continuous flow - Organ Recovery Systems LifePort - each single kidney in self-contained perfusion system. For the kidney allograft assessment will be used measurements performed during machine perfusion in hypothermia: renal flow, resistance, lactate dehydrogenase, lactates and ischemia injury markers measured in the fourth hour of perfusion in perfusion fluid. For kidney ischemia injury assessment such markers will be measured: tumour necrosis factor (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1), neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3. Every time from pair of retrieved kidneys each kidney will be randomise for one of the group: group 1) - 50 kidneys - examined group - cured with etanercept (ENBREL) in the first hour of perfusion by adding drug to perfusion fluid, group 2) - 50 kidneys - control group - without intervention. Ischemia injury markers will be measured in perfusion fluid by kidney two times (in the first and fourth hour of perfusion) for assessment of efficacy kidney ischemia injury decreasing. Results of measurements of kidney ischemia injury before transplantation, parameters during machine perfusion in hypothermia and donor parameters will be correlated with kidney allograft function post transplantation. Immediate, delayed and slow graft function, primary non-function, kidney function assessed by creatinine concentration and creatinine clearance at one day, seven days, two weeks, 1, 6 and 12 months post transplantation and kidney graft survival 6 and 12 months post transplantation will be analysed.

Official Title
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Limitation of Ischemic Injury of a Kidney Stored in Machine Perfusion in Hypothermia - Evaluation of the Impact on Kidney Allograft Function

Conditions
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Transplanted Kidney Ischemia Reperfusion Injury

Intervention / Treatment
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* Drug: etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DONOR STAGE donor after brain death seronegative HCV (hepatitis C virus) procurement of two kidneys from the same donor donor center distance up to 220 kilometres from Warsaw availability of fluid KPS-1 and cartridge of Organ Recovery System RECIPIENT STAGE recipient of kidneys from deceased donor at least eighteen recipient expression of informed consent Exclusion Criteria: DONOR STAGE live kidney donor seropositive HCV (hepatitis C virus) get only one from the kidneys doubtful donor - e.g. need for biopsy because of proteinuria or due to histological lesions (e.g. tumor) donor center distance above 220 kilometres from Warsaw lack of fluid KPS-1 and cartridge of Organ Recovery System RECIPIENT STAGE recipient of kidney form living donor minor recipient no expression of informed consent multiple organ recipient recipient EN BLOC kidneys or two kidneys recipient of kidney from donor under 14 years old a need of atypical urinary diversion in kidney recipient participation in another study at least in the last 30 days

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept<br> | Drug: etanercept<br>* adding appropriate dose of etanercept to the perfusion fluid<br>|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delayed graft function | a need at least one dialysis during first week after transplantation | one week | 
| 12 months graft survival | survival of kidney grafts 12 months after transplantation | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute rejection | biopsy proven acute rejection episodes during the first year after transplantation | 12 months | 
| kidney ischemia injury assessment | ischemia injury markers measured two times (in the first and fourth hour of perfusion) in perfusion fluid: tumour necrosis factor (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1), neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3 | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemia, reperfusion, kidney, transplantation