Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial

Background Vitamin D defciency is associated with increased risks of mortality in people with chronic kidney disease. The benefts and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the efectiveness of calcifediol in reducing mortality in patients with vitamin D insufciency on hemodialysis compared to no additional therapy. Methods A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insuffciency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. Results Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confdence interval (CI) 0.63–1.67]. Calcifediol had no detectable efects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. Conclusions In adults treated with hemodialysis and who had vitamin D insufciency, calcifediol supplementation for 24 months had inconclusive efects on mortality and cardiovascular outcomes.