Biochemical Parameters After Cholecalciferol Repletion in Hemodialysis: Results From the VitaDial Randomized Trial

Background: The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D-3 (25[OH] D) levels < 30 ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol. Study Design: 2-center, double-blind, randomized, 13-week, controlled trial followed by a 26-week open-label study. Setting & Participants: 55 adult maintenance hemodialysis patients with 25(OH) D levels < 30 ng/mL were recruited from June 2008 through October 2009. Intervention: Cholecalciferol, 25,000 IU, per week orally versus placebo for 13 weeks, then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. Outcomes: Primary end point was the percentage of patients with 25(OH) D levels >= 30 ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D. Measurements: Blood calcium and phosphate were measured weekly; iPTH, 25(OH) D, 1,25-dihydroxyvitamin D-3 (1,25[OH](2)D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39. Results: The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P < 0.001), as well as 1,25(OH)(2)D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10-15] pg/mL; P < 0.001) and the proportion of patients achieving the target calcium level (76.9% vs 48.2%; P = 0.03). Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The second 26-week study phase did not significantly modify the prevalence of 25(OH) D level >= 30 ng/mL in patients issued from the placebo group. Limitations: Small size of the study population. Conclusions: Oral weekly administration of 25,000 IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)(2)D levels in hemodialysis patients. Further evaluation of clinical end points is suggested. (C) 2014 by the National Kidney Foundation, Inc.