A randomized trial of cholecalciferol versus doxercalciferol for lowering parathyroid hormone in chronic kidney disease.

BACKGROUND AND OBJECTIVES: The optimal treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized, blinded, 3-month trial in vitamin D-deficient CKD stage 3 and 4 patients with parathyroid hormone (PTH) values above the Kidney Disease Outcomes Quality Initiative target, comparing cholecalciferol (4000 IU/d x 1 month, then 2000 IU/d; n = 22) to doxercalciferol (1 microg/d; n = 25). RESULTS: There was no difference in baseline demographics or lab tests, except a slightly higher estimated GFR (eGFR) in the doxercalciferol group. There was a significant increase in vitamin D level in the cholecalciferol group (14 +/- 6 to 37 +/- 10 ng/ml; P < 0.001) but no change in the doxercalciferol group. The PTH decreased by 27% +/- 34% in the doxercalciferol group (P = 0.002) and decreased by 10% +/- 31% in the cholecalciferol group (P = 0.16), but the difference between treatments was NS (P = 0.11). Similar results were found when absolute PTH change from baseline to end point was analyzed in a repeated-measures ANOVA model. The serum calcium and urine calcium excretions were not different. Additional non-mineral-related end points, albuminuria, and BP were evaluated, and although trends were present, this did not reach significance. CONCLUSIONS: This prospective, randomized trial demonstrated a within-group reduction in PTH in the doxercalciferol-treated patients but no significant difference between the doxercalciferol and cholecalciferol patients. Larger, long-term studies are needed to demonstrate efficacy of mineral-related and non-mineral-related end points and safety.

Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States.

BACKGROUND: Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion. METHODS: Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L). RESULTS: Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). CONCLUSION: This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.