The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease

Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53 ml/min per 1.73 m(2), PTH 46 pg/ml, FGF23 42 pg/ml, and 25(OH)vitamin D3 53 nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of >= 40 ml/min per 1.73 m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status.