Expression and Function of Hepatic Drug Metabolizing Enzymes and Transport Proteins in Livers of Patients with End‐Stage Renal Disease (ESRD)
Bibliographic record
Abstract
Objectives This study aims to determine the changes in expression and function of hepatic drug metabolizing enzymes (DMEs) and drug transport proteins in liver samples from patients with end‐stage renal disease (ESRD). Methods Liver samples were collected from nine recently deceased patients with ESRD and six recently deceased controls. Relative gene expression of DMEs and transport proteins were determined by qPCR. Results P‐gp and CYP2E1 expression were significantly decreased (P<0.05) in ESRD livers compared to control livers (21% and 17% of control, respectively). There was a trend of decreased expression of CYP2D6, CYP2C9, OATP1B1 MRP2 and MRP3, although this failed to reach significance. Conclusions Our results demonstrate that DMEs and transport proteins are down‐regulated in ESRD. Current studies are evaluating the enzymatic activity of DMEs in hepatic microsomes from ESRD patients using the specific probe substrates midazolam (CYP3A4), tolbutamide (CYP2C9), chlorzoxazone (CYP2E1) and dextromethorphan (CYP2D6). Our results help explain the large decrease in non‐renal drug clearance observed in patients with ESRD. This research is supported by the Lawson Health Research Institute.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".