TY - JOUR
T1 - Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol
AU - Alshayeb, Hala
AU - Showkat, Arif
AU - Wall, Barry M.
AU - Gyamlani, Geeta G.
AU - David, Valentin
AU - Quarles, L. Darryl
N1 - Publisher Copyright:
Copyright © 2014 by the Endocrine Society.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Context: The optimal circulating concentration of 25(OH) vitamin D is controversial.Objective: The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement.Design: Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m2 (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14).Setting: The study was conducted at the Veterans Affairs clinics.Main Outcome Measure: Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment.Results: Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P =.001; 12.2 ± 9 ηg/mL, P =.0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P =.0024; 1.0 ± 0.72 ηg/mL P =.0002), and reduced serum PTH (-11 ±21 pg/mL, P =.0292; -42 ± 68 pg/mL, P =.0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P =.01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mLP ≤.05) without changing 24,25(OH)2D, FGF-23 or PTH levels.Conclusion: Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.
AB - Context: The optimal circulating concentration of 25(OH) vitamin D is controversial.Objective: The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement.Design: Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m2 (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14).Setting: The study was conducted at the Veterans Affairs clinics.Main Outcome Measure: Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment.Results: Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P =.001; 12.2 ± 9 ηg/mL, P =.0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P =.0024; 1.0 ± 0.72 ηg/mL P =.0002), and reduced serum PTH (-11 ±21 pg/mL, P =.0292; -42 ± 68 pg/mL, P =.0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P =.01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mLP ≤.05) without changing 24,25(OH)2D, FGF-23 or PTH levels.Conclusion: Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.
UR - http://www.scopus.com/inward/record.url?scp=84907611809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907611809&partnerID=8YFLogxK
U2 - 10.1210/jc.2014-1308
DO - 10.1210/jc.2014-1308
M3 - Article
C2 - 24960544
AN - SCOPUS:84907611809
SN - 0021-972X
VL - 99
SP - E1830-E1837
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 10
ER -
