Assessment of 24,25(OH) 2 D levels does not support FGF23-mediated catabolism of vitamin D metabolites

Bing Dai, Valentin David, Hala M. Alshayeb, Arif Showkat, Geeta Gyamlani, Ronald L. Horst, Barry Wall, Leigh Quarles

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Abstract

Progressive elevations of fibroblastic growth factor 23 (FGF23) in chronic kidney disease may reduce serum 25-hydroxyvitamin D (25(OH)) and 1,25-dihydroxyvitamin D (1,25(OH)2 D) levels, via stimulation of 24-hydroxylase (Cyp24a1)-mediated catabolism of these vitamin D metabolites. To test this possibility, we measured serum concentrations of 24,25- dihydroxyvitamin D (24,25(OH)2 D), a product of Cyp24a1 hydroxylation of 25(OH)D, in the Col4a3 knockout mouse, a model of Alport syndrome-derived chronic kidney disease, and in patients with chronic kidney disease of variable severity. There was an inverse correlation between serum FGF23 and both 25(OH)D and 1,25(OH)2 D in the mouse model, but no significant relationship was observed in the cross-sectional patient cohort. The FGF23-dependent increase in Cyp24a1 mRNA expression in the mouse kidneys was consistent with the possibility that FGF23 induces vitamin D catabolism. There was, however, a reduction in serum 24,25(OH)2 D levels, rather than the expected elevation, in both the mice and patients with chronic kidney disease. Low 25(OH)D and elevated FGF23 and parathyroid hormone levels were correlated with the reduced serum 24,25(OH)2 D concentrations of these patients. Thus, we failed to find support for FGF23-mediated catabolism of vitamin D metabolites in chronic kidney disease assessed by 24,25(OH)2 D levels.

Original languageEnglish (US)
Pages (from-to)1061-1070
Number of pages10
JournalKidney International
Volume82
Issue number10
DOIs
StatePublished - Nov 2 2012

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Vitamin D
Intercellular Signaling Peptides and Proteins
Chronic Renal Insufficiency
Serum
Hereditary Nephritis
Dihydroxycholecalciferols
Hydroxylation
Mixed Function Oxygenases
Parathyroid Hormone
Knockout Mice
Kidney
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Nephrology

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Assessment of 24,25(OH) 2 D levels does not support FGF23-mediated catabolism of vitamin D metabolites. / Dai, Bing; David, Valentin; Alshayeb, Hala M.; Showkat, Arif; Gyamlani, Geeta; Horst, Ronald L.; Wall, Barry; Quarles, Leigh.

In: Kidney International, Vol. 82, No. 10, 02.11.2012, p. 1061-1070.

Research output: Contribution to journalArticle

Dai, Bing ; David, Valentin ; Alshayeb, Hala M. ; Showkat, Arif ; Gyamlani, Geeta ; Horst, Ronald L. ; Wall, Barry ; Quarles, Leigh. / Assessment of 24,25(OH) 2 D levels does not support FGF23-mediated catabolism of vitamin D metabolites. In: Kidney International. 2012 ; Vol. 82, No. 10. pp. 1061-1070.
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