Osteoprotegerin/RANKL axis and progression of coronary artery calcification in hemodialysis patients

Clin J Am Soc Nephrol. 2012 Jun;7(6):965-73. doi: 10.2215/CJN.11191111. Epub 2012 Apr 5.

Abstract

Background and objectives: Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.

Design, setting, participants, & measurements: Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.

Results: Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.

Conclusions: Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Chi-Square Distribution
  • Chronic Disease
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / etiology*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Kidney Diseases / blood
  • Kidney Diseases / complications
  • Kidney Diseases / therapy*
  • Linear Models
  • Male
  • Middle Aged
  • Osteoprotegerin / blood*
  • Prospective Studies
  • RANK Ligand / blood*
  • Renal Dialysis / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Turkey
  • Vascular Calcification / blood
  • Vascular Calcification / etiology*

Substances

  • Biomarkers
  • Inflammation Mediators
  • Osteoprotegerin
  • RANK Ligand
  • TNFRSF11B protein, human
  • TNFSF11 protein, human