Uridine Diphosphate (UDP) Sugars Predict AKI in Cardiac Surgery Patients
Bibliographic record
Abstract
Background: UDP-sugars including UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal), UDP-N-acetylgalactosamine (UDP-GalNAc), UDP-N-acetylglucosamine (UDP-GlcNAc), and UDP-glucuronic acid (UDP-GlcA) activate the pro-inflammatory P2Y14 receptor. Previously, we showed elevated urine UDP-Glc in intensive care unit patients with AKI compared to those without AKI. In addition, renal ischemia reperfusion injury in mice led to an increase in UDP-Glc urine concentration, followed by activation of P2Y14 in intercalated cells (ICs), initiating an inflammatory cascade that worsened AKI. Ischemic-AKI is prevalent among cardiac surgery patients. Here we investigated whether UDP-sugars serve as early markers of AKI in these patients. Methods: Urine and plasma samples were collected from 53 cardiac surgery patients: prior to initiation of cardio-pulmonary bypass (CPB), at the end of CPB, and 4h, 12h, 24h, 48h, and 72h post-CPB. The concentration of UDP-sugars was quantified using mass spectrometry. The ROC-AUC was used to evaluate the association between urinary and plasma UDP-sugars and AKI. Correlation analysis was performed with urinary kidney injury molecule -1 (KIM-1), measured by electroluminescence. Results: Compared to patients without AKI, urinary concentration of UDP-Glc (P=0.002), UDP-Gal (P=0.001) and UDP-GalNAc/GlcNAc (P= 0.0001) increased 12h post-CPB, followed by a return to reference levels in patients diagnosed with AKI 24h after surgery. Urinary UDP-GlcA and plasma UDP-sugars did not vary with AKI. Optimal threshold values of UDP-Glc, UDP-Gal, UDP-GalNAc/GlcNAc, and their sum, predicted AKI with AUC values of 0.71, 0.72, 0.75 and 0.76, respectively. Urinary levels of UDP-Glc and UDP-Gal correlated with KIM-1 at 12h post-CPB (R > 0.43). Conclusion: Our findings indicate that UDP-Glc, UDP-Gal and UDP-GalNAc/GlcNAc measured in urine are predictors of AKI. Given the correlation observed between KIM-1 - a marker indicative of proximal tubule (PT) injury - and UDP-Glc and UDP-Gal, we suggest that these UDP-sugars are actively released by damaged PT during CPB. Following their release, they are eliminated in the urine, where they trigger the activation of the P2Y14 receptor in ICs. This study, thus, identifies P2Y14 as a key driver in AKI. Funding: Government Support – Non-U.S.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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".