Defects in KIM-1-Mediated Phagocytosis Do Not Predispose to AKI in Humans
Bibliographic record
Abstract
Background: Phagocytosis of dying cells is critical for homeostasis and tissue repair. During renal injury, upregulation of kidney injury molecule-1 (KIM-1) transforms kidney epithelial cells into phagocytes which engulf apoptotic and necrotic cells. A mutation that impairs KIM-1 phagocytic function (mucin domain deletion) resulted in worse kidney dysfunction after ischemia-reperfusion-injury (IRI) in mice, but this has not been studied in humans. Methods: We expressed three common mucin domain nonsynonymous variants (rs12522248, rs45439103, rs6149307) of the human KIM-1 gene (HAVCR1) in human kidney cells. To test if impaired KIM-1-mediated phagocytosis predisposes to kidney dysfunction after IRI, we genotyped 627 consecutive kidney donors and assessed risk of delayed graft function in recipients. Results: Cells expressing these variants exhibited markedly reduced phagocytosis of apoptotic and necrotic cells, compared to cells expressing wild type KIM-1; rs6149307 showed the most severe defects (<5% phagocytosis vs. wild type). Surprisingly, the risk of delayed graft function in recipients of donor kidneys homozygous for rs6149307 was not significantly increased compared to recipients of donor kidneys with one or no copies (adjusted relative risk 1.0 [0.7-1.3]). Analysis of rs12522248 and rs45439103 yielded similar resutls. Conclusions: Contrary to murine models, these results suggest severe defects in KIM-1-mediated phagocytosis do not predispose to acute kidney dysfunction after IRI in humans. Funding: Government Support - Non-U.S.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".