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

Abstract

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.

Figure 1.

Percent change in PTH over time. The percent change in intact PTH levels over the course of the study is graphed for subjects treated with cholecalciferol (solid circles, solid line) and doxercalciferol (solid triangles, dashed line). The numbers of subjects for months 0, 1, 2, and 3 were 22, 22, 20, and 20, respectively, for the cholecalciferol arm, and 25, 24, 21, and 20 for the doxercalciferol arm.

Figure 2.

Change in calcium over time. The change in calcium levels over the course of the study is graphed for subjects treated with cholecalciferol (solid circles, solid line) and doxercalciferol (solid triangles, dashed line). The numbers of subjects for months 0, 1, 2, and 3 were 22, 22, 20, and 20, respectively, for the cholecalciferol arm, and 25, 24, 21, and 20 for the doxercalciferol arm.

Figure 3.

Change in phosphorus over time. The change in phosphorus levels over the course of the study is graphed for subjects treated with cholecalciferol (solid circles, solid line) and doxercalciferol (solid triangles, dashed line). The numbers of subjects for months 0, 1, 2, and 3 were 22, 22, 20, and 20, respectively, for the cholecalciferol arm, and 25, 24, 21, and 20 for the doxercalciferol arm.