Vitamin D deficiency has been linked to cardiovascular events and mortality, infection, and autoimmune disorders [Nigwekar SU et al. Am J Kidney Dis. 2012]. Deficiency of 25-hydroxyvitamin D [25(OH)D] < 30 ng/mL occurs in about 80% of patients undergoing dialysis. Retrospective observational studies in dialysis have shown mixed results of 25(OH)D supplementation on parathyroid hormone (PTH) and erythropoiesis-stimulating agent use. Clinical trials of 25(OH)D supplementation showed mixed results, were limited by small numbers of patients, and showed no effect on outcomes.

Dana C. Miskulin, MD, Tufts Medical Center, Boston, Massachusetts, USA, reported on Safety and Effects of Supplementation With Ergocalciferol on Erythropoietin Dosing in Hemodialysis Patients [NCT01395823], a double-blind, placebo-controlled trial to confirm safety and determine the effects of dosing on dialysis patients.

Patients who were receiving dialysis, on a stable erythropoietin (EPO) dose, with no impairment to oral 25(OH)D absorption, and deficient in 25(OH)D (< 30 ng/mL) were eligible. Ergocalciferol doses were determined using baseline 25(OH)D levels.

Study outcomes included changes in doses of EPO, 1,25(OH)2D, and phosphate binders; changes in levels of calcium, phosphorous, PTH, and C-reactive protein (CRP); use of cinacalcet; and incidence of hypercalcemia or hyperphosphatemia, all-cause hospitalization, infectious hospitalization, total infections, falls, and fractures.

Eligible patients with baseline 25(OH)D < 30 ng/mL (n = 276) were randomly assigned to placebo (n = 139) or ergocalciferol (n = 137). In both the treatment and placebo groups, there were 4 deaths and 15 patients dropped out. The 2 groups were well balanced for demographic characteristics, including age (median 61 years), sex, race, 25(OH)D levels and dose, and EPO dose; about 80% were taking active vitamin D.

Mean 25(OH)D levels increased to 40 ng/mL at 3 months and to 38 ng/mL at 6 months in the ergocalciferol group compared with the placebo group (P < .0001). For patients with a baseline 25(OH)D of 16 to 30 ng/mL, there was an increase at 3 months but a decline at 6 months; however, 25(OH)D levels remained significantly increased (P < .0001).

There was no significant difference (P = .76) between placebo and ergocalciferol in the change in EPO dose or change in PTH (P = .60). In addition, there were no significant changes in calcium, phosphorous, calcitriol dose, phosphate binder use, cinacalcet use, or CRP levels or significant differences between groups in all-cause hospitalization, cardiovascular hospitalization, infectious hospitalization, total infections, falls, and fracture events.

The only significant difference between groups was in doxercalciferol; the change in micrograms/treatment/month for the ergocalciferol group was 0.21 (95% CI, 0.10 to 0.31) and for the placebo group was 0.04 (−0.06 to 0.15; P = .02). However, Dr Miskulin did not consider this to be clinically significant.

Although it was the largest randomized controlled trial of vitamin D supplementation in patients on dialysis, this study was subject to limitations, including a high percentage of black patients (n = 160), who have lower total 25(OH)D levels than whites [Powe CE et al. N Engl J Med. 2013], although in a subgroup analysis, no differences by race were found for any outcome.

Supplementation with 25(OH)D to achieve levels ≥ 30 ng/mL in patients on dialysis is safe, but in this short, underpowered study, it does not appear to offer any benefits.