Urinary UDP-Glucose as a Novel Actionable Biomarker of Dehydration-Induced AKI
Bibliographic record
Abstract
Background: People working in “extreme” conditions such as sugar cane workers, firefighters, and military personnel are subjected to significant dehydration. Prolonged episodes of dehydration may result in acute kidney Injury (AKI). AKI is associated with inflammation and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. We showed that the P2Y14 receptor mediates renal inflammation leading to AKI following ischemia-reperfusion-injury. P2Y14 is activated by the danger molecule UDP-glucose (UDP-Glc). Here we hypothesized that UDP-Glc is released by damaged cells throughout the body after dehydration-induced stress. UDP-Glc is filtered by the kidney and concentrated in collecting ducts where it activates P2Y14 in intercalated cells. This would trigger renal inflammation and contribute to dehydration-associated AKI. Methods: Mice were subjected to water deprivation for 24, 48 and 72 hours. Kidney function was assessed via serum creatinine (SCr), blood urea nitrogen (BUN) and urine albumin. To study proximal tubule (PT) damage, aquaporin 1 (AQP1) localization was analyzed by immunofluorescence (IF). Urinary UDP-Glc concentration was measured by LC-MS, and renal recruitment of immune cells by flow cytometry and IF. Results: Mice that were subjected to dehydration showed body weight loss. Water deprivation induced elevations in SCr and BUN after 48 and 72 hours, relative to control. Dehydration also promoted albuminuria and the redistribution of AQP1 from the plasma membrane into the PT cell body indicating PT injury. An increase in urinary UDP-Glc concentration, and renal recruitment of macrophages (CD64+F4/80+) were detected at 48 and 72 hours of dehydration. In particular, infiltration of CD11c-positive renal macrophages after dehydration was observed. Conclusions: This study supports the hypothesis that UDP-Glc, released by damaged cells during severe dehydration, induces the renal recruitment of inflammatory macrophages leading to PT injury. Blocking the UDP-Glc/P2Y14 pathway represents, therefore, a new therapeutic avenue for the attenuation of dehydration-induced renal inflammation and dysfunction. In this context, urinary UDP-Glc is a promising actionable biomarker for dehydration-induced AKI. Funding: NIDDK Support, Commercial Support - Danone Nutricia Research
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".