SP301PREFERENTIAL VASCULAR DEPOSITION OF TISSUE PHOSPHATE LINKED TO IMPAIRED PHOSPHATE KINETICS LEADS TO CALCIFICATION IN EXPERIMENTAL CHRONIC KIDNEY DISEASE
Bibliographic record
Abstract
Introduction and Aims: Pathogenic vascular calcification (VC), a process linked to altered phosphate metabolism, is a marker of advancing CVD in CKD patients. Despite the critical role of phosphate in cell biology, there are significant gaps in knowledge regarding the in vivo kinetics of circulating phosphate. The study objective was to characterize the changes in phosphate tissue distribution that could underlie the vascular pathogenesis seen in experimental CKD (SD rats, 7 wks 0.25% adenine in diet). Methods: Phosphate distribution was assessed by determining tissue 33-PO4 (radio labeled) levels 20 minutes following an infusion of phosphate (100 mM via left jugular vein). Blood levels were taken at 2 time points (T=0, 20 min via the right jugular vein). After sacrifice, 33-PO4 levels were determined in 50 tissues (e.g. vascular, skeletal muscle, organs, fat, bone). Results: The 7 weeks of adenine treatment generated significant renal dysfunction, (creatinine = 345±15 vs. 27±8.4 uM) and hyperphosphatemia (5.43±1.7 vs. 1.5±0.26 mM) compare to controls (n=5). CKD rats were stratified into two groups based on the presence (n=6, VC+) or absence (n=7, VC-) of abdominal aorta calcification (Ca2+ >20nmol/mg tissue). Serum creatinine, phosphate, calcium and plasma FGF-23 levels were similar between the two CKD groups (VC+, VC-) at baseline. In CKD rats, serum 33-PO4 was >3 fold elevated (p<0.05) immediately post 33-PO4 infusion compared to controls. At 20 minutes post infusion, serum 33-PO4 levels remained significantly elevated only in the CKD (VC-) group compared to control (p<0.05). FGF-23 did not change due to the acute phosphate infusion in either CKD or control animals. The distribution pattern of 33-PO4 was markedly different between groups. In particular, all vascular phosphate uptake was significantly increased in CKD-VC+ rats (3-100 fold) compared to CKD-VC- (p<0.05). Although not as extreme as in CKD-VC+ rats, the distribution of phosphate in CKD-VC- rats also significantly shifted from non-vascular tissues (kidney cortex, medulla, fat pads) towards the vasculature, when compared to controls. In addition, some tissue segments (aorta, iliac and carotid artery, kidney cortex, left ventricle, skeletal muscle and femur) from healthy and CKD rats were placed in vitro (DMEM, 3.8mM PO4 containing 33PO4, 60 minutes) to determine whether the tissue transport phenotype had been altered. The in vitro findings corroborated the in vivo findings; that is, in vascular segments from CKD VC+ animals, but not in other tissues (skeletal muscle, bone), 33-PO4 uptake was significantly increased: aorta (1.9x), iliac (3.7x) and carotid artery (3.8x; p<0.05).
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".