Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation.
BACKGROUND
Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation.


METHODS
The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years).


RESULTS
Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6. 52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up.


CONCLUSIONS
Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.
Schnuelle
P
P
Fifth Medical Clinic (Nephrology, Endocrinology), University Hospital Mannheim, Germany. schnuell@rumms.uni-mannheim.de
Lorenz
D
D
Mueller
A
A
Trede
M
M
Van Der Woude
F J
FJ
D000208:Acute Disease; D000328:Adult; D001926:Brain Death; D002102:Cadaver; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D004298:Dopamine / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
D002316:Cardiotonic Agents; D004298:Dopamine