Donor Dopamine and Initial Graft Function
Information source: University Hospital Mannheim
Information obtained from ClinicalTrials.gov on November 03, 2008
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
Sponsored by: University Hospital Mannheim
Official(s) and/or principal investigator(s):
Peter Schnuelle, MD, Principal Investigator, Affiliation: University Hospital Mannheim
Fokko J van der Woude, MD, PhD, Study Chair, Affiliation: University Hospital 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
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
Official title: Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: Requirement of hemodialysis post-transplant
Incidence and severity of acute rejection episodes
S-creatinine on days 1-7 post transplant
Patient and graft survival
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
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.
Minimum age: 18 Years.
Maximum age: N/A.
- Brain death confirmed
- Given consent to organ donation
- Current s-creatinine < 2mg/dl
- On admission s-creatinine < 1. 3mg/dl
- Age over 18 years
- Placed on the waiting list
- Organ allocation according to ET standards
- Application of dopamine/dobutamine/adrenaline
- Application of noradrenaline > 0. 4µg/kg*min
- Hemodynamic instability
- Refusal to participate in study /data analysis
Locations and Contacts
University Hospital Mannheim, Mannheim, Baden-Wuerttemberg 68135, Germany; Recruiting
Peter Schnuelle, MD, Phone: 0049 621 383 2751, Email: firstname.lastname@example.org
Benito A Yard, PhD, Phone: 0049 621 383 3212, Email: email@example.com
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, Gottmann U, Xiao Y, Breedijk A, Wandschneider S, Losel 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
Ending date: March 2009
Last updated: June 6, 2008