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Donor Dopamine and Initial Graft Function

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

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00115115
Enrollment
487
Registered
2005-06-21
Start date
2004-03-31
Completion date
2009-03-31
Last updated
2009-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ESRD, Kidney Transplantation

Keywords

Donor dopamine, Immediate graft function, Kidney transplantation

Brief summary

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

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.

Interventions

DRUGDopamine 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

Sponsors

Eurotransplant International Foundation, Leiden, The Netherlands
CollaboratorOTHER
Regional Organ Procurement Organization (DSO), Baden-Wuerttemberg, Germany
CollaboratorOTHER
Regional Organ Procurement Organization (DSO), Bavaria, Germany
CollaboratorOTHER
Novartis
CollaboratorINDUSTRY
Universitätsmedizin Mannheim
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frame
Requirement of hemodialysis post-transplantwithin 1 week after surgery

Secondary

MeasureTime frame
Incidence and severity of acute rejection episodeswithin the first 30 days (plus minus 3 days) after surgery
S-creatinine on days 1-7 post transplantwithin the first week after transplantation
Patient and graft survivalafter 12, 24 and 36 months post-transplant

Countries

Germany

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Apr 2, 2026