FP452ALTERATIONS OF THE VITAMIN D METABOLOME IN CKD PATIENTS REVEALS IMPAIRED STATUS NOT REFLECTED BY 25(OH)D3
Bibliographic record
Abstract
INTRODUCTION: Clinical assessment of 25(OH)D3 assesses dietary sufficiency and likely has limited utility in capturing the significant alterations in vitamin D metabolism in CKD patients, that contributes to mineral bone disorder in these patients. Degradation of both active vitamin D (1,25(OH)2D3) and its precursor (25(OH)D3) predominantly occurs through 24-hydroxylation, catalyzed by CYP24A1. The substrate-to-product ratio between vitamin D metabolites and their 24-hydroxylated catabolite estimates the activity of this enzyme on a global level. This study sought to characterize a comprehensive vitamin D metabolome and catabolism through vitamin D metabolite (VDM) ratios of 25(OH)D3and 1,25(OH)2D3(1) across a range of kidney function in a cohort of participants with gold-standard inulin-measured GFR and (2) with or without pharmacological treatment of 1,25(OH)2D3in a cohort of hemodialysis (HD) patients. METHODS: GFR was measured via urinary inulin clearance. Phosphate, calcium and PTH were measured at Kingston Health Science Center (Roche Diagnostics) and FGF-23 was measured in duplicate using an ELISA (Kainos). Serum vitamin D metabolites were measured by LC-MS/MS, involving sample preparation by liquid-liquid extraction, immunoextraction, and derivatization with DMEQ-TAD. RESULTS: Participants had a range of kidney function with measured GFR that ranged from 9 to 148 mL/min (n=84) or HD (n=90). There was no difference in circulating 25D across the range of kidney function (25.9±10.1 ng/mL, p=0.2) or dialysis patients (27.2±12.0 ng/mL). However, there was a significant increase in the VDM-ratio 25(OH)D3:24,25(OH)2D3 as GFR declined, withthe highest found in HD patients. This higher 25(OH)D3:24,25(OH)2D3VDM ratio, indicative of decreased catabolism, was also associated with PTH with and without adjustment for age and GFR (r=0.3, p<0.05). An assessment of 1-alpha hydroxylated metabolites did not exhibit similar patterns of catabolism. GFR was inversely associated with1,25(OH)2D3(r=0.5, p<0.001) and 1,24,25(OH)3D3(r=0.3, p<0.05) but was not associated with the VDM-ratio. After adjustment for age and GFR, FGF-23 was inversely associated with the 1,25(OH)2D3:1,24,25(OH)3D3VDM-ratio (r=-0.4, p<0.05). In HD patients, the 1,25(OH)2D3:1,24,25(OH)3D3VDM-ratio was inversely associated with dialysis vintage and calcitriol use and dose. The calcitriol-treated HD patients (N=56, 64%) had no difference in their 25-D metabolome, with similar levels of 25(OH)D3, 24,25(OH)2D3 and no difference in the 25(OH)D3:24,25(OH)2D3 VDM ratio compared to non-treated patients. Calcitriol-treated patients had significantly higher levels of 1,25(OH)2D3, however similar levels of its catabolite, resulting in a doubling of the ratio between 1,25(OH)2D3and 1,24,25(OH)3D3. CONCLUSIONS: Catabolism of 25(OH)D3, but not 1,25(OH)2D3, was clearly altered in non-dialysis CKD. These significant alterations in D status were not reflected by changes in the clinically measured vitamin D metabolite. The results also suggest that, in HD patients, exogenous 1,25(OH)2D3 is catabolized differently than that which is endogenously produced.The substrate-to-product ratio between vitamin D metabolites may indicate tissue-based metabolism, and therefore be a better indicator of vitamin D status not reflected by clinically measured circulating vitamin D levels.
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 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".