Intragraft tacrolimus: The missing link in heart transplant acute rejection monitoring

Monitoring systemic Tacrolimus (TAC) concentrations in whole blood (WB) is the clinical standard for heart transplant recipients, yet it often fails to accurately reflect drug exposure within the graft. This study investigated TAC concentrations directly in endomyocardial biopsies (EMBs) from 43 de novo heart transplant patients over a one-year follow-up. While WB levels remained within the therapeutic range (5-20 ng/mL) for all patients, 11 episodes of acute rejection (grade 2R) occurred. Statistical analysis revealed no significant difference in WB profiles between rejecting and non-rejecting groups. Conversely, TAC levels within the EMBs showed significant divergence, particularly at three months post-transplant, with rejecting patients exhibiting markedly lower tissue concentrations. These findings suggest that intragraft TAC levels, potentially modulated by donor-specific P-glycoprotein expression, provide superior diagnostic insight compared to systemic monitoring, offering a more precise tool for personalizing immunosuppressive therapy and predicting rejection.