Donor Dopamine and Initial Graft Function

Study Overview
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Brief Summary
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Donor pre-treatment with dopamine reduces injury to the kidney graft with consequences on the clinical performance immediately after transplantation: Donor dopamine reduces the requirement of dialysis post transplant, and results in renal function improvements. The purpose of the study is to investigate the potentially therapeutic impact of donor preconditioning with low dose dopamine in human renal transplant recipients from a brain dead donor.

Detailed Description
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During the transplantation process, the kidney graft is exposed to numerous events which may in turn lead to function deteriorations. In particular, factors related with brain death, like hemodynamic instability and systemic release of cytokines, cold preservation upon harvesting, and reperfusion injury accumulate in harm conveying a pro-inflammatory state to the graft before transplantation. Early graft dysfunction has long-term consequences. Renal transplants with delayed graft function and acute rejection have a greater incidence of chronic dysfunction. Allorecognition is induced when the host immune system detects alloantigens in the context of danger signals. Reducing danger signals through medical donor management may therefore have a considerable impact on the transplantation outcomes. In a case control study from the Transplantation Center of Mannheim, Germany, donor use of both dopamine and noradrenaline during intensive care before organ retrieval was associated with less acute rejection episodes after transplantation and resulted in superior long-term graft survival. Donor employment of catecholamines remained predictive of an improved graft survival probability even after controlling for various confounding factors like age, gender, cold ischemia, HLA matching and immunosuppressive medication. This observation has been confirmed by a larger retrospective cohort study based on the Eurotransplant registry, including 2404 kidney transplants performed at 47 renal transplantation centers in 1993. The salutary effect on the graft function rate at 4 years exhibited a dose-response relationship and compared in quantitative terms with prospective HLA matching on class I or II antigens. Besides these long-term benefits, donor preconditioning with dopamine is associated with improvements of immediate graft function after kidney transplantation. Donor dopamine was associated with less requirement of hemodialysis and more rapid recovery of graft function posttransplant in a single centre study involving 254 consecutive renal transplant recipients. Implementing dopamine as a therapeutic tool in the management of cadaver kidney donors may have a major impact on both immediate graft function and long-term graft survival without adverse side effects for the recipients.

Official Title
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Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation

Conditions
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Kidney Transplantation, ESRD

Intervention / Treatment
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* Drug: Dopamine infusion to brain dead organ donors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Donors: Brain death confirmed Given consent to organ donation Current s-creatinine < 2mg/dl On admission s-creatinine < 1.3mg/dl Recipients: Age over 18 years Placed on the waiting list Organ allocation according to ET standards Exclusion Criteria: Donors: Application of dopamine/dobutamine/adrenaline Application of noradrenaline > 0.4µg/kg*min Hemodynamic instability Recipients: Refusal to participate in study /data analysis Pregnancy

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: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dopamine infusion to brain dead organ donors|Dopamine infusion administered at a dosage of 4µg/kg/min starting after brain death has been proven until to surgical procurement of the kidneys|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Requirement of hemodialysis post-transplant |  | within 1 week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of acute rejection episodes |  | within the first 30 days (plus minus 3 days) after surgery | 
| S-creatinine on days 1-7 post transplant |  | within the first week after transplantation | 
| Patient and graft survival |  | after 12, 24 and 36 months post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor dopamine, Immediate graft function, Kidney transplantation