A prospective cohort conversion study of twice-daily to once-daily extended-release tacrolimus: role of ethnicity
Bibliographic record
Abstract
BACKGROUND: Tacrolimus is a widely used calcineurin inhibitor in kidney transplantation. It is available as twice-daily Prograf® (Tac-BID) and once-daily Advagraf® (Tac-OD). Although therapeutically equivalent, some patients require dose adjustments to achieve similar trough concentrations [C0] after conversion. Tacrolimus exposure is affected by ethnicity in the de novo setting but the role of ethnicity in determining dose requirements and adjustments after conversion is unknown. METHODS: In this study, 496 renal transplant recipients (RTRs) were prospectively converted from Tac-BID to Tac-OD, with dose adjustments targeted to achieve similar [C0] at 12 months post-conversion. Renal function, acute rejection and Tac dose adjustments by ethnicity were analyzed. RESULTS: There were similar numbers of recipients from living and deceased donors. The mean transplant duration was 7 years. Of the RTRs, 60% were Caucasian and 40% were identified as belonging to an ethnic minority. There was no change in estimated renal function (eGFR) post-conversion to Tac-OD. At 12 months, 35/488 (7%) RTRs were receiving a reduced dose, 101/488 (21%) required a dose increase of which 77 (16%) were receiving at least a 30% increase in dose over baseline. The percentage of those in ethnic groups requiring a dose increase of >30% varied from 8.0% for South Asians to 27.5% for East Asians (P = 0.03), despite East Asians having a similar baseline dose of Tac-BID (3.59 mg/day) compared to the entire cohort (3.53 mg/day). CONCLUSIONS: Ethnicity may play an important role in dosing requirements when converting from Tac-BID to Tac-OD, unrelated to baseline dose. Further investigation is required to determine the reasons for ethnic variability when patients are converted between tacrolimus preparations.
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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 | 0.001 |
| 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".