[Tacrolimus blood levels and incidence of graft rejection in heart transplantation].
OBJECTIVE
To determine the relationship between pharmacokinetic parameters and clinical outcomes after heart transplantation and to determine the range of tacrolimus blood levels which provides the most effective protection against graft rejection. To study other factors that predict graft rejection.


METHODS
We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 2000 and October 2003 and had routine monitoring of tacrolimus trough levels at the time of scheduled endomyocardial biopsy. Rejection was defined as Grade = 3, based on the International Society for Heart and Lung Transplantation (ISHLT) criteria. The follow-up period was 1 year. All patients were on a triple therapy regimen of Tacrolimus (TAC), Corticosteroids and Azatioprine/Micophenolate Mofetil. Data were analyzed by Student s t-test, univariate logistic regression and ROC curve.


RESULTS
Tacrolimus blood levels measured at day +5 postransplant were the strongest predictor of acute graft rejection over a 1-year follow-up period (rejection 5.76 +/- 3.4 ng/ml vs no rejection 9.66 +/- 2.73 ng/ml, p = 0.016). A decrease of one unit in TAC trough level values at day +5 postransplant implied a 1.58 greater risk of rejection (p = 0.05). Overall incidence of treated acute rejection was lower for patients with trough levels higher than 8 ng/ml on day +5 postransplant (33 vs 80%, p = 0.055, Fisher s exact test).


CONCLUSIONS
Data suggest that in heart transplant patients it may be crucial to achieve tacrolimus levels of at least 8 ng/ml during the first days postsurgery to avoid rejection.
Albornoz López
R
R
Servicio de Farmacia, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, Spain.
Aumente Rubio
M D
MD
Arizón Del Prado
J M
JM
Cárdenas Aranzana
M
M
López Malo de Molina
M D
MD
Gago Sánchez
A I
AI
D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016559:Tacrolimus