Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial
Luigi Morrone, Suetonia C. Palmer, Valeria Saglimbene, Annalisa Perna, Giuseppe Cianciolo, Domenico Russo, Loreto Gesualdo, Patrizia Natale, Antonio Santoro, Sandro Mazzaferro, Mario Cozzolino, Adamasco Cupisti, Marina Di Luca, Biagio Di Iorio, Giovanni FM Strippoli, the Mineral Metabolism Study Group of the Italian Society of Nephrology, Carlo Massimetti, Fabio Pennacchiotti, Antonio Mannarino, Cristina Grimaldi, Vincenzo Savica, Onofrio Schillaci, Olga Credentino, M. Casu, Carlo Lomonte, Valentina Vigo, Giuseppe Grandaliano, Stefano Netti, Filippo Aucella, Massimo Morosetti, R Boero, Francesco Soleti, Efstratios Fasianos, Maria Polidoro, Domenico Santoro, Alessandra Perna, Fabio Malberti, Ludovica D’Apice, Romano Musacchio, Massimiliano Porcu, Giuseppe Cianciolo, Silverio Rotondi, Maria Luisa Muci
Abstract
BACKGROUND: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. METHODS: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency 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% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects 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 insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. TRIAL REGISTRATION NUMBER: NCT01457001.