Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study

Abstract

Objective: To investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD).

Methods: In this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2), vitamin D insufficiency (serum 25[OH]D <30 ng/mL), and serum intact PTH levels >70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time.

Results: Geometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol-treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07).

Conclusion: Weekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD.

Fig. 1

Geometric mean for serum 25-hydroxyvitamin D (25[OH]D) concentrations in patients with stage 3 and 4 chronic kidney disease treated with placebo or cholecalciferol, 50 000 IU once weekly, for 12 weeks. Serum 25(OH)D levels were measured as a marker of vitamin D status in participants treated with placebo (diamonds) or cholecalciferol (squares) at baseline, 6 weeks, and 12 weeks of the study. The response profiles of cholecalciferol-treated and placebo-treated patients are significantly different starting at 6 weeks and at 12 weeks (P<.001) as indicated by the asterisks. Error bars indicate 95% confidence intervals.

Fig. 2

Geometric mean for serum parathyroid hormone (PTH) concentrations in patients with stage 3 and 4 chronic kidney disease treated with placebo or cholecalciferol, 50 000 IU once weekly, for 12 weeks. Serum PTH levels were measured in participants treated with placebo (diamonds) or cholecalciferol (squares) at baseline, 6 weeks, and 12 weeks of the study. The PTH levels of the 2 study groups are not significantly different at each of the 3 time points (P = .14). Error bars indicate 95% confidence intervals.