Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation

Background Epidemiological data implicate that renal transplants from livin g unrelated donors result in superior survival rates as compared with cadav eric grafts, despite a higher degree of human lymphocyte antigen (HLA) mism atching. We undertook a center-based case control study to identify donor-s pecific determinants affecting early outcome in cadaveric transplantation. Methods. The study database consisted of 152 consecutive cadaveric renal tr ansplants 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 rule s of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-b ased triple-drug regimen. In 67 recipients, at least one acute rejection ep isode occurred during the first month after transplantation. They were take n as cases, and the remaining 85 patients were the controls. Stepwise logis tic regression was done on donor-specific explanatory variables obtained fr om standardized Eurotransplant Necrokidney reports. In a secondary evaluati on, the impact on graft survival in long-term follow-up was further measure d 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 mismatc h on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increase d 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) independ ently 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 s ignificant predictor of superior graft survival in long-term follow-up. Conclusions. Our data strongly suggest that the use of catecholamines in po stmortal organ donors during intensive care results in immunomodulating eff ects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic s ubstances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.