High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial

Abstract

Background: Vitamin D deficiency contributes to secondary hyperparathyroidism, which occurs early in chronic kidney disease (CKD).

Objectives: We aimed to determine whether high-dose cholecalciferol supplementation for 1 y in early CKD is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration ≥30 ng/mL) and decrease serum parathyroid hormone (PTH). A secondary aim was to determine the effect of cholecalciferol on blood pressure and serum fibroblast growth factor-23 (FGF23).

Design: This was a double-blind, randomized, placebo-controlled trial. Forty-six subjects with early CKD (stages 2-3) were supplemented with oral cholecalciferol (vitamin D group; 50,000 IU/wk for 12 wk followed by 50,000 IU every other week for 40 wk) or a matching placebo for 1 y.

Results: By 12 wk, serum 25(OH)D increased in the vitamin D group only [baseline (mean ± SD): 26.7 ± 6.8 to 42.8 ± 16.9 ng/mL; P < 0.05] and remained elevated at 1 y (group-by-time interaction: P < 0.001). PTH decreased from baseline only in the vitamin D group (baseline: 89.1 ± 49.3 to 70.1 ± 24.8 pg/mL; P = 0.01) at 12 wk, but values were not significantly different from baseline at 1 y (75.4 ± 29.5 pg/mL; P = 0.16; group-by-time interaction: P = 0.09). Group differences were more pronounced in participants with secondary hyperparathyroidism (group-by-time interaction: P = 0.004). Blood pressure and FGF23 did not change in either group.

Conclusions: After 1 y, this oral cholecalciferol regimen was safe and sufficient to maintain serum 25(OH)D concentrations and prevent vitamin D insufficiency in early CKD. Furthermore, serum PTH improved after cholecalciferol treatment, particularly in patients who had secondary hyperparathyroidism.

Trial registration: ClinicalTrials.gov NCT00427037.

Figures

FIGURE 1.

Flow diagram of participant enrollment. Subjects with stage 2–3 chronic kidney disease (n = 79) were screened for participation in the study. Forty-eight subjects were randomly assigned to receive a placebo or vitamin D. Two subjects did not receive their allocated intervention; data are presented in only the 46 participants who received treatment. Thirty-seven subjects completed the 1-y study and were included in the final analysis.

FIGURE 2.

Least-squares mean (±SEM) serum 25(OH)D concentrations in early chronic kidney disease subjects who were randomly assigned to receive vitamin D or a placebo for 1 y. Subjects with early-stage chronic kidney disease (mean eGFR: 62 ± 15 mL · min−1 · 1.73 m−2) were randomly assigned to receive 50,000 IU vitamin D/wk for 12 wk followed by 50,000 IU vitamin D every other week for 40 wk (n = 22) or an identically matched placebo (n = 24). Serum 25(OH)D concentrations are reported across time and by treatment group. The vitamin D group (solid line) had a significant increase in serum 25(OH)D by 12 wk, which remained elevated from baseline at 52 wk. The placebo group (dashed line) had a significant decrease in 25(OH)D by 12 wk. The group*time was determined with mixed-model repeated-measures ANOVA. *Significant change from baseline, P < 0.05 (paired t test); asignificant difference from placebo, P < 0.05 (t test). eGFR, estimated glomerular filtration rate; group*time, group-by-time interaction; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3.

Percentage of vitamin D–insufficient participants by treatment and week. The prevalence of vitamin D insufficiency in the vitamin D group (n = 22; black bars) was reduced by weeks 12 and 52. The vitamin D–insufficiency prevalence was higher in the placebo group (n = 24; white bars) than in the vitamin D group at weeks 12 (P < 0.001; chi-square test) and 52 (P = 0.08, chi-square test). 25(OH)D, 25-hydroxyvitamin D.

FIGURE 4.

Least-squares mean (±SEM) PTH concentrations across time by treatment group in patients with chronic kidney disease who were randomly assigned to receive vitamin D or a placebo for 1 y. Subjects with early-stage chronic kidney disease (mean PTH concentration at baseline 83.4 ± 37.8 pg/mL) were randomly assigned to receive 50,000 IU vitamin D/wk for 12 wk followed by 50,000 IU vitamin D every other week for 40 wk (n = 22) or an identically matched placebo (n = 24). Serum PTH concentrations are reported across time and by treatment group. Serum PTH concentrations decreased from baseline at 12 wk in the vitamin D group (solid line) and did not change in the placebo group (dashed line). *Significant difference from baseline, P < 0.05 (paired t test). The group*time was determined with mixed-model repeated-measures ANOVA. group*time, group-by-time interaction; PTH, parathyroid hormone.

FIGURE 5.

Least-squares mean (±SEM) percentage changes in PTH concentrations from baseline by time and treatment group in patients with elevated baseline PTH concentrations (>70 pg/mL) adjusted for baseline 25(OH)D concentrations. Compared with placebo group (n = 24, dashed line), the vitamin D group (n = 22; solid line) experienced a significantly greater percentage decrease in PTH at weeks 12 and 52. *P-group difference < 0.05 (ANCOVA). group*time, group-by-time interaction. PTH, parathyroid hormone.