Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels?

Deficiency of 1,25-dihydroxyvitamin D [1,25(OH)₂D] and excessive fibroblast growth factor (FGF23) are suggested to be associated with increased mortality in patients with chronic kidney disease (CKD). Generally, 24-hydroxylation has been considered the first step in the degradation pathway of 1,25(OH)₂D and 25(OH)D. 24,25-dihydroxyvitamin D [24,25(OH)₂D] was believed to be a degradation product, with no important biological effects. However, some data have accumulated showing that 24,25(OH)₂D has biological effects on its own. Under conditions of eucalcemia, the synthesis of 24,25(OH)₂D is increased, and the synthesis of 1,25(OH)₂D is decreased. In patients with CKD, both high parathyroid hormone levels, which decrease the activity of enzyme CYP24A1 (24-hydroxylase), and high FGF23 levels, which increase the activity of enzyme CYP24A1, were often detected. However, information about 24,25(OH)₂D levels in these patients is very limited. Whether compensatory changes in levels of FGF23 and 24,25(OH)₂D in CKD patients are protective or harmful remain unknown issues. Therefore, more studies are needed to identify the nature of the interactions between these molecules and to fully elucidate their clinical significance.