CHOLECALCIFEROL (VITA MIN D 3 ) THERAPY AND VITAMIN D INSUFFICIENCY IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RANDOMIZED CONTROLLED PILOT STUDY

Objective— To investigate the efficacy of cholecalciferol (vitamin D 3 ) 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 m 2 ), 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. In patients with CKD, several small studies have evaluated ergocalciferol to correct vitamin D insufficiency. Many of these studies have been retrospective analyses, which demonstrate variable results in the effectiveness of ergocalciferol in reducing PTH values in patients with CKD. A study to evaluate the effectiveness of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines found that only about 60% of participants with stage 3 and 4 CKD who were given ergocalciferol therapy (up to 50 000 IU weekly) reached 25(OH)D levels greater than 30 ng/mL (28). The ergocalciferol therapy resulted in a 13% decrease and 2% increase in PTH level in participants with stage 3 and 4 CKD, respectively (28). Pesenson et al retrospectively evaluated 45 patients with CKD who were mildly vitamin-D insufficient (mean serum 25(OH)D concentration of 26.1 ng/mL) and who were treated with ergocalciferol in wide range of dosages over a 6-month period The investigators found that serum 25(OH) D levels increased only slightly (mean of 8.1 ng/mL) and, as expected, that there was no change in PTH values from baseline assessment. In a similar retrospective study, Shah et al reported that treatment with various regimens of ergo-calciferol did not decrease PTH values significantly (30). In a larger study of 85 patients with stage 3 to 5 CKD, Thorp et al reported that PTH levels decreased significantly (about 16%) after 12 weeks of ergocalciferol therapy ranging from a mean daily dosage of 800 IU to 7100 IU (31). In another study, patients with CKD receiving peritoneal dialysis who were given 50 000 IU ergocalciferol per week for 4 weeks had only a 7% decrease in PTH levels Thus, ergocalciferol therapy in CKD is generally modestly effective in correcting vitamin D nutriture and/or the current dosing recommendations are inadequate to reach target levels established by the National Kidney Foundation.