Cholecalciferol vs. Small Doses of Alfacalcidol vs. Placebo in Chronic Kidney Disease Patients on Hemodialysis: A...

The ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 μg/week) or placebo, given for 12 weeks, on serum 1,25(OH)₂D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment.

This was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D <20 ng/ml, iPTH <1,000 ->110 pg/ml, calcium <10.2, and phosphate <6.8 mg/dl. The subjects were stratified by serum iPTH, then randomized into 3 groups according to the treatment.

To our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)₂D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)₂D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters.

In most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 μg/week dose of alfacalcidol in rising serum 1,25(OH)₂D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.