Comparison of the novel HK-2 human renal proximal tubular cell line with the standard LLC-PK1 cell line in studying drug-induced nephrotoxicity
Bibliographic record
Abstract
Established cell lines are widely used as in vitro models in toxicology studies. The choice of an appropriate cell line is critical when performing studies to elucidate drug-induced toxicity in humans. The porcine renal proximal tubular cell line LLC-PK1 is routinely used to study the nephrotoxic effects of drugs in humans. However, there are significant interspecies differences in drug pharmacokinetics and pharmacodynamics. The objective of this study was to determine whether the human renal proximal tubular cell line HK-2 is an acceptable model to use when performing in vitro toxicity studies to predict effects in humans. We examined 2 nephrotoxic agents, ifosfamide (IFO) and acyclovir, that exhibit different clinical nephrotoxic patterns. HK-2 cells metabolized IFO to its nephrotoxic metabolite, chloroacetaldehyde (CAA). Acyclovir induced a concentration-dependent decrease in HK-2 cell viability, suggesting that acyclovir may induce direct insult to renal proximal tubular cells. The results support clinical pathology data in humans and suggest that HK-2 cells are a suitable model to use in in vitro toxicity studies to determine drug-induced nephrotoxicity in humans.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".