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Bone Abstracts (2016) 5 P469 | DOI: 10.1530/boneabs.5.P469

1University of East Anglia, Norwich, Norfolk, UK; 2Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK.

Fibroblast growth factor-23 (FGF23) is a major regulator of phosphate metabolism often elevated in genetic hypophosphataemic disorders and in chronic kidney disease–bone mineral disorder (CKD–BMD). Recent studies have identified relationships between FGF23 and vitamin D.

Objectives: To determine the relationship between vitamin D and FGF23 metabolism in CKD.

Method: We used randomized samples from patients with CKD (eGFR <70) and volunteers from the Ministry of Defense were used as controls. FGF23 concentrations were measured using an enzyme-linked immunosorbent assay for cFGF23 (Biomedica, Vienna, Austria) and for iFGF23 (Immutopics Inc., San Clemente, CA, USA). 25(OH)D (D2 and D3) and 24,25(OH)2D3 were measured by LCMS.

Results: cFGF23 concentrations were significantly higher in CKD patient samples (7.2±2.5) than controls (1.47±2.1 pg/ml). Low iron status was observed, 37% of CKD patients showed low iron concentration (13.8±1.8 μmol/l; norm 11.5–30 μmol/l) and a transferrin saturation <16%; 24% showed elevated ferritin with values >300 μg/l. Decreasing eGFR (from 70 to 20) was accompanied by a small decrease in vitamin D status, 25(OH)D from 60 to 40 nmol/l and 24,25(OH)2D3 from 4 to 1 nmol/l; while the ratio of 25(OH)D:24,25(OH)2D3 (mean 23±1) increased.

Conclusion: cFGF23 is raised in patients with CKD as a compensatory response to hyperphosphatemia or phosphate overload. Due to 25(OH)D deficiency, patients with CKD develop secondary hyperparathyroidism which exacerbates bone loss bone disease. 24-hydroxylase, enzyme responsible for the catabolism of both 25(OH)D and 1,25(OH)2D, is rapidly induced by 1,25(OH)2D and FGF-23 and suppressed by parathyroid hormone (PTH). In CKD, net effects of declining renal function and rising FGF23 and PTH concentrations on vitamin D catabolism are not clear. We observed that 24,25(OH)2D3 concentrations are further suppressed in CKD patient with vitamin D deficiency, suggesting metabolism favours the production of biologically active 1,25(OH)2D.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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