JHLT open · 2025
Association between tacrolimus blood levels and biopsy-proven acute cellular rejection in adult heart transplant recipients.
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Yang Chengliang, Shannon Casey P, Assadian Sara, Lapp Linda, Nair Rithika, Huan Tao, Partovi Nilu, Toma Mustafa, Tebbutt Scott J
Аннотация
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.
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.