The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

Nephrol Dial Transplant. 2008 Oct;23(10):3263-71. doi: 10.1093/ndt/gfn226. Epub 2008 May 7.

Abstract

Background: Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies.

Methods: We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures.

Results: Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, beta = -0.45, model R(2) = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, beta = -0.29 and P = 0.014, ss = 0.33, respectively, model R(2) = 32%).

Conclusions: This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Flow Velocity
  • Blood Proteins / metabolism*
  • Blood Vessels / pathology*
  • Blood Vessels / physiopathology*
  • Calcinosis / pathology*
  • Calcinosis / prevention & control
  • Calcium-Binding Proteins / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy
  • Male
  • Osteoprotegerin / blood*
  • Renal Dialysis*
  • alpha-2-HS-Glycoprotein

Substances

  • AHSG protein, human
  • Blood Proteins
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Osteoprotegerin
  • TNFRSF11B protein, human
  • alpha-2-HS-Glycoprotein
  • matrix Gla protein