Association between tacrolimus blood levels and biopsy-proven acute cellular rejection in adult heart transplant recipients
Bibliographic record
Abstract
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 (LC-MS/MS). Patients were stratified into two post-transplant intervals: 0-90 days and 91-180 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/day; p = 0.047). Clinical review confirmed no concurrent cytomegalovirus (CMV) 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".