Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial

Clin J Am Soc Nephrol. 2017 Sep 7;12(9):1438-1446. doi: 10.2215/CJN.01870217. Epub 2017 Aug 7.

Abstract

Background and objectives: High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD.

Design, setting, participants, & measurements: We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m2and serum 25-hydroxyvitamin D level <30 ng/ml at the University of Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 μg) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation.

Results: One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m2, respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P<0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P=0.004).

Conclusions: Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD.

Keywords: 25-hydroxyvitamin D; Adult; Brachial Artery; Calcifediol; Calcitriol; Cholecalciferol; Dilatation; Double-Blind Method; Humans; Inflammation; Minerals; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamins; chronic kidney disease; clinical trial; glomerular filtration rate; parathyroid hormone; vascular disease.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Brachial Artery / drug effects*
  • Brachial Artery / metabolism
  • Brachial Artery / physiopathology
  • Calcitriol / adverse effects
  • Calcitriol / therapeutic use*
  • Cholecalciferol / adverse effects
  • Cholecalciferol / therapeutic use*
  • Colorado
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Inflammation Mediators / blood
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Recovery of Function
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Biomarkers
  • Inflammation Mediators
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D
  • Calcitriol