The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report

Clin J Am Soc Nephrol. 2010 Apr;5(4):568-75. doi: 10.2215/CJN.07081009. Epub 2010 Feb 4.

Abstract

Background and objectives: Vitamin K-dependent matrix Gla protein (MGP) acts as a calcification inhibitor in vitro and in vivo. The present study was performed to (1) determine plasma levels of the inactive, dephosphorylated, uncarboxylated MGP (dp-ucMGP) in a cohort of patients at different stages of chronic kidney disease (CKD) and (2) evaluate the association between dp-ucMGP levels on one hand and aortic calcification and mortality on the other.

Design, setting, participants, & measurements: 107 patients (67 +/- 13 years; 60% male; 32% at CKD stages 2 to 3, 31% at stages 4 to 5, 37% at stage 5D) were assayed for dp-ucMGP and underwent multislice spiral computed tomography scans to quantify aortic calcification at baseline. They were prospectively monitored for mortality.

Results: Plasma dp-ucMGP levels augmented progressively with CKD stage, with a significant difference from CKD stage 4. CKD stage, hemoglobin, age, and coumarin use were independently associated with plasma dp-ucMGP levels. Furthermore, plasma dp-ucMGP and age were positively and independently associated with the aortic calcification score. During follow-up (802 +/- 311 days), 34 patients died (20 from cardiovascular events). In a crude analysis, [plasma dp-ucMGP] > 921 pM was associated with overall mortality; this association was lost after adjusting for both age and the calculated propensity score.

Conclusions: Plasma dp-ucMGP increased progressively in a CKD setting and was associated with the severity of aortic calcification. Plasma dp-ucMGP could thus be a surrogate marker for vascular calcification in CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Diseases / blood*
  • Aortic Diseases / diagnostic imaging
  • Aortic Diseases / mortality
  • Aortography / methods
  • Biomarkers / blood
  • Calcinosis / blood*
  • Calcinosis / diagnostic imaging
  • Calcinosis / mortality
  • Calcium-Binding Proteins / blood*
  • Chi-Square Distribution
  • Chronic Disease
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases / blood*
  • Kidney Diseases / diagnostic imaging
  • Kidney Diseases / mortality
  • Linear Models
  • Male
  • Matrix Gla Protein
  • Middle Aged
  • Pilot Projects
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Tomography, Spiral Computed
  • Up-Regulation

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins