The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D 3 and 1,25(OH) 2 D 3 in a cross-sectional analysis of participants with a range of kidney function assessed by...

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Veröffentlicht in:Scientific reports 2022-06, Vol.12 (1), p.10925-10925, Article 10925
Hauptverfasser: Turner, Mandy E., Rowsell, Tyler S., White, Christine A., Kaufmann, Martin, Norman, Patrick A., Neville, Kathryn, Petkovich, Martin, Jones, Glenville, Adams, Michael A., Holden, Rachel M.
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Sprache:eng
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Zusammenfassung:Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D 3 and 1,25(OH) 2 D 3 in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N = 143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC–MS/MS. Circulating measures of 24-hydroxylation of 25(OH)D 3 (24,25(OH) 2 D 3 :25(OH)D 3 ) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3: 1,25(OH) 2 D 3 vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH) 3 D 3 , despite no increase of 1,25(OH) 2 D 3 . This first report of circulating 1,24,25(OH) 3 D 3 in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-15033-9