Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients

Chronic kidney disease-associated mineral and bone disorder is believed to be precipitated by declining renal 1α-hydroxylase activity resulting in decreased conversion of 25-hydroxyvitamin D (25[OH]D) to active 1,25-dihydroxyvitamin D (1,25[OH]₂D). The majority of circulating 25(OH)D and 1.25(OH)₂D is bound to vitamin D binding protein (DBP) and, to a lesser extent, albumin, with less than 1% circulating in the unbound form. The free hormone hypothesis suggests that free hormones show far greater biological activity than their protein bound counterparts. The aim of this study was to determine whether ‘bioavailable’ vitamin D associates more strongly with measures of mineral metabolism than total vitamin D in patients undergoing haemodialysis.

Ninety-four subjects were identified from a subgroup of the Accelerated Mortality on Renal Replacement (ArMORR) cohort of incident haemodialysis patients, who had previously had 25(OH)D and 1,25(OH)₂D measured as part of a case-control survival study. An approximately equal number of black and white controls, and race-matched cases, were randomly selected. Subjects had not been on activated vitamin D, ergocalciferol or cholecalciferol prior to initiation of dialysis. DBP was measured on stored serum and bioavailable 25(OH)D and 1,25(OH₂)D were calculated using previously validated formulae.

Bioavailable, but not total, 25(OH)D and 1,25(OH₂)D, were found to correlate significantly with adjusted calcium. Univariate and multivariate regression analysis (with age, gender, race, survival at one year, calcium, phosphorus and bioavailable 1,25[OH]₂D) showed that only bioavailable 25(OH)D correlated with parathyroid hormone. This study confirmed previous findings that black subjects have lower concentrations of total 25(OH)D; however, no difference was found in concentrations of bioavailable 25(OH)D between black and white subjects.

The authors conclude that bioavailable vitamin D concentrations are better correlated with measures of mineral metabolism than total concentrations in patients on haemodialysis. This builds upon a previous study by the same group which showed similar findings in healthy subjects.