Association between tacrolimus blood levels and biopsy-proven acute cellular rejection in adult heart transplant recipients

Background

Acute cellular rejection (ACR) is a common complication following heart transplantation (HTx). This study examined the association between tacrolimus whole-blood concentrations and endomyocardial biopsy (EMB)-proven ACR in adult HTx recipients.

Methods

We conducted a retrospective analysis of 41 adult HTx recipients enrolled in the HEARTBiT study at St. Paul’s Hospital (Vancouver, Canada) between August 2018 and February 2020. A total of 315 EMB visits were analyzed and matched with tacrolimus whole-blood trough concentrations measured within ±1 day using liquid chromatography-tandem mass spectrometry. Patients were stratified into 2 post-transplant intervals: 0 to 90 days and 91 to 180 days, based on BC Clinical Guidelines for Transplant Medications for target tacrolimus levels.

Results

During the first 90 days post transplant, tacrolimus concentrations were significantly lower in 2R rejection episodes compared to both 0R (p = 0.006) and 1R (p = 0.013) groups. No significant differences in tacrolimus levels were observed beyond 90 days. In a linear mixed effects model adjusting for time post transplant (days) and tacrolimus dose, 2R rejection remained independently associated with lower tacrolimus concentrations (−2.73 µg/ml; p = 0.021), despite slightly higher dosing at those visits (+0.10 mg/d; p = 0.047). Clinical review confirmed no concurrent cytomegalovirus infections or major changes in other immunosuppressive therapies.

Conclusions

Lower tacrolimus concentrations during moderate ACR episodes were not attributable to underdosing or clinical confounders, suggesting the role of altered pharmacokinetics or patient-specific factors. Taken together, our results emphasize the clinical relevance of tailoring tacrolimus targets to individual pharmacokinetics, especially in early-phase post-transplant care.