Abstract
Vascular calcification which induces advanced atherosclerosis is a serious problem in hemodialysis patients. Fetuin-A (alpha 2-Heremans-Schmid glycoprotein) is synthesized by liver cells and has anti-calcification effects. Especially, in hemodialysis patients, fetuin-A is associated with malnutrition, inflammation, and atherosclerosis. In this study, to clarify the association between the extent of atherosclerosis and fetuin-A concentrations, we investigated carotid ultrasonography longitudinally. The study included 78 hemodialysis patients aged 59.5 years, with a duration of hemodialysis of 90.9 months. In 2005 and 2008, we measured intima media thickness including plaques of the bilateral common carotid arteries using B-mode ultrasonography to evaluate atherosclerosis quantitatively, and observed the status of calcification. We defined the sum of both intima media thicknesses as IMT. Serum fetuin-A concentrations were determined by ELISA in 2008. The IMT of the calcification(+) group showed a significantly greater increase than the calcification(-) group. However, fetuin-A concentrations were not significantly different between the two groups. Then, we divided all subjects into two groups according to the level of fetuin-A (=0.235±0.043 g/L). ΔIMT in the lower fetuin-A group (<0.24 g/L) was significantly greater than that in the higher fetuin-A (≥0.24 g/L) group (p=0.022). During a 3-year follow-up period, the calcification progressed in 18 patients. Fifteen of these patients were in the lower fetuin-A group and 3 were in the higher fetuin-A group. In the lower fetuin-A group, the progression of carotid arterial calcification occurred with high frequency (p=0.001). Although there was no correlation between fetuin-A and IMT in data collected during 2005 or 2008. However, there was an inverse correlation between fetuin-A and ΔIMT (r=-0.276, p=0.014). Therefore, we considered that the current serum level of fetuin-A reflectes the earlier progression of atherosclerosis. These findings demonstrate that a lower level of fetuin-A concentrations is related to calcification and thickening of the intima media of the carotid artery in hemodialysis patients.
