The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis

Nephrol Dial Transplant. 2011 Apr;26(4):1327-39. doi: 10.1093/ndt/gfq725. Epub 2010 Dec 8.

Abstract

Background: This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone.

Methods: Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 μg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52.

Results: Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve.

Conclusions: In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcinosis / drug therapy*
  • Calcinosis / etiology
  • Cinacalcet
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / etiology
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperparathyroidism, Secondary / etiology
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Naphthalenes / therapeutic use*
  • Prognosis
  • Prospective Studies
  • Renal Dialysis*
  • Vitamin D / therapeutic use*
  • Vitamins / therapeutic use

Substances

  • Naphthalenes
  • Vitamins
  • Vitamin D
  • Cinacalcet