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Donor Dopamine and Initial Graft Function

Information source: Universitätsmedizin Mannheim
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Kidney Transplantation; ESRD

Intervention: Dopamine infusion to brain dead organ donors (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Universitätsmedizin Mannheim

Official(s) and/or principal investigator(s):
Peter Schnuelle, MD, Principal Investigator, Affiliation: Universitätsmedizin Mannheim
Fokko J van der Woude, MD, PhD, Study Chair, Affiliation: Universitätsmedizin Mannheim
Werner Lauchart, MD, Study Director, Affiliation: Organ procurement organization (DSO) of Baden-Wuerttemberg
Detlef Boesebeck, MD, Study Director, Affiliation: Organ procurement organization (DSO) of Bavaria

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Requirement of hemodialysis post-transplant

Secondary outcome:

Incidence and severity of acute rejection episodes

S-creatinine on days 1-7 post transplant

Patient and graft survival

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

University Hospital Mannheim, Mannheim, Baden-Wuerttemberg 68135, Germany
Additional Information

Related publications:

Schnuelle P, Yard BA, Braun C, Dominguez-Fernandez E, Schaub M, Birck R, Sturm J, Post S, van der Woude FJ. Impact of donor dopamine on immediate graft function after kidney transplantation. Am J Transplant. 2004 Mar;4(3):419-26.

Yard B, Beck G, Schnuelle P, Braun C, Schaub M, Bechtler M, Göttmann U, Xiao Y, Breedijk A, Wandschneider S, Lösel R, Sponer G, Wehling M, van der Woude FJ. Prevention of cold-preservation injury of cultured endothelial cells by catecholamines and related compounds. Am J Transplant. 2004 Jan;4(1):22-30.

Schnuelle P, Berger S, de Boer J, Persijn G, van der Woude FJ. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation. 2001 Aug 15;72(3):455-63.

Schnuelle P, Lorenz D, Mueller A, Trede M, Van Der Woude FJ. Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int. 1999 Aug;56(2):738-46.

Starting date: March 2004
Last updated: April 22, 2009

Page last updated: August 23, 2015

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