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

Kidney Int. 2012 Nov;82(10):1061-70. doi: 10.1038/ki.2012.222. Epub 2012 Jun 27.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Aged
  • Animals
  • Autoantigens / genetics
  • Biomarkers / blood
  • Chi-Square Distribution
  • Collagen Type IV / deficiency
  • Collagen Type IV / genetics
  • Cross-Sectional Studies
  • Dihydroxycholecalciferols / blood*
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Fibroblast Growth Factors / blood*
  • Humans
  • Hydroxylation
  • Kidney / enzymology
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Nephritis, Hereditary / blood*
  • Nephritis, Hereditary / enzymology
  • Parathyroid Hormone / blood
  • RNA, Messenger / metabolism
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / enzymology
  • Severity of Illness Index
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Up-Regulation
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D3 24-Hydroxylase

Substances

  • Autoantigens
  • Biomarkers
  • Collagen Type IV
  • Dihydroxycholecalciferols
  • PTH protein, human
  • Parathyroid Hormone
  • RNA, Messenger
  • type IV collagen alpha3 chain
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • 25-hydroxyvitamin D
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Cyp24a1 protein, mouse
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase