Nutritional vitamin D supplementation in dialysis: a randomized trial

Abstract

Background and objectives: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is common in patients initiating long-term hemodialysis, but the safety and efficacy of nutritional vitamin D supplementation in this population remain uncertain.

Design, setting, participants, & measurements: This randomized, placebo-controlled, parallel-group multicenter trial compared two doses of ergocalciferol with placebo between October 2009 and March 2013. Hemodialysis patients (n=105) with 25(OH)D levels ≤32 ng/ml from 32 centers in the Northeast United States were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of the 12-week treatment period. Survival was assessed through 1 year.

Results: Baseline characteristics were similar across all arms, with overall mean±SD 25(OH)D levels of 21.9±6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo) (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8±2.3 ng/ml; P<0.001) and monthly (38.3±2.4 ng/ml; P=0.001) arms compared with placebo (27.4±2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and active vitamin D treatment did not differ between groups. All-cause and cause-specific hospitalizations and adverse events were similar between groups during the intervention period. Lower all-cause mortality among ergocalciferol-treated participants was not statistically significant (hazard ratio, 0.28; 95% confidence interval, 0.07 to 1.19).

Conclusions: Oral ergocalciferol can increase 25(OH)D levels in incident hemodialysis patients without significant alterations in blood calcium, phosphate, or parathyroid hormone during a 12-week period.

Keywords: ESRD; clinical trial; dialysis; vitamin D.

Copyright © 2015 by the American Society of Nephrology.

Figures

Figure 1.

Patient enrollment in the Dialysis Infection and Vitamin D in New England (DIVINE) study. *In addition to explicit exclusion criteria, patient's primary provider or the investigator could exclude a patient from enrollment if participation was felt to be too complex for the patient or logistically impractical (e.g., because of travel). 25(OH)D, 25-hydroxyvitamin D; Ergo, ergocalciferol.

Figure 2.

Ergocalciferol (Ergo) treatment: effects on 25-hydroxyvitamin D (25[OH]D levels, calcium, phosphate, and parathyroid hormone (PTH). Participants receiving 50,000 IU of ergocalciferol weekly exhibited the greatest increase in 25(OH)D level, although levels remained higher in both ergocalciferol arms compared with the placebo group. Figures show adjusted mean values and 95% confidence intervals of the estimate. PTH and its 95% confidence interval were exponentiated from natural log–transformed estimates.

Figure 3.

Effects of ergocalciferol (Ergo) treatment on PTH values by active vitamin D use. Treatment arm assignment did not affect PTH levels, regardless of use of active vitamin D. Active vitamin D use was defined as treatment with calcitriol, paricalcitol, or doxercalciferol at three or more study visits. Figures show adjusted mean values and 95% confidence intervals of the estimate. PTH and its 95% confidence interval were exponentiated from natural log–transformed estimates.