FP452ALTERATIONS OF THE VITAMIN D METABOLOME IN CKD PATIENTS REVEALS IMPAIRED STATUS NOT REFLECTED BY 25(OH)D3
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».