P450 Oxidoreductase *28 (POR*28) and Tacrolimus Disposition in Pediatric Kidney Transplant Recipients—A Pilot Study
Bibliographic record
Abstract
BACKGROUND: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in pediatric kidney transplant recipients. In a recent study in adults, POR*28 was associated with increased dosing requirements early after transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed to evaluate the additional contribution of POR*28 to early tacrolimus disposition in pediatric kidney transplant recipients. METHODS: Retrospective data of 43 pediatric kidney transplant recipients up to 14 days posttransplant were evaluated on tacrolimus dose and tacrolimus predose blood concentrations. Recipient POR*28 and CYP3A5 genotype were determined. RESULTS: CYP3A5 expressers carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5 expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between POR genotypes. CONCLUSIONS: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding should be validated in a larger population, and it would be worthwhile to evaluate the clinical impact of this genotype.
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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 | 0.000 | 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".