**6. Evaluation of vascular calcification**

that functions as a new inhibitor of calcium-phosphate deposition [49], suppresses calcinosis by binding hydroxyapatite [50], and protects VSMCs from the harmful effects of calcium overload and subsequent calcification [51]. Fetuin-A suppresses VSMC apoptosis through death-signaling pathways: (i) it is internalized by VSMCs, concentrated in intracellular vesicles, and secreted via vesicle release from apoptotic and living VSMCs; (ii) fetuin-A in vesicles suppresses their ability to nucleate calcium phosphate; and (iii) fetuin-A increases phagocytosis of vesicles by VSMCs. These results confirm finding that the internalization of fetuin-A into VSMCs is a key finding in the inhibition of vesicle-mediated VSMC calcification [51]. In *in vitro* experiments, fetuin-A has been reported to antagonize the action of TGF-*β*1 (transforming growth factor-β1) and inhibit osteogenesis and calcium-containing matrix deposition in dexamethasone-treated rat bone marrow cells [49]. Moreover, fetuin-A-KO mice show severe ectopic calcinosis in the myocardium, kidney, lung, tongue, and skin [49]. A recent study [49] demonstrated that ESRD patients who had lower serum fetuin-A concentrations showed a lower survival rate from cardiovascular diseases, indicating that fetuin-A is related

Matrix Gla protein (MGP) is a matrix protein that was firstly discovered from bone [52], and it is an important modulator of vascular calcification. To exert its biological activity, MGP requires to be activated through interaction with vitamin K [53]. The calcification of cartilage and blood vessels has been found to be inhibited by MGP [54]. MGP affects on vascular calcification directly by reducing calcium crystal formation and indirectly by modulating transcription factors that suppress VSMC transformation to the osteoblast-like cells [55]. Moreover, MGP is an important factor capable of transformation of VSMCs [58]. A decrease in glomerular filtration rate has been shown to result in a reduction in

The receptor activator of nuclear factor *κ*-light-chain-enhancer of activated B-cells (RANK), and RANK ligand (RANKL), and osteoprotegerin (OPG) might be associated with the mechanism of vascular calcification. RANKL functions are inhibited by OPG that acts as a decoy receptor to inhibit RANKL/RANK relationships [57]. This system may be related to the imbalance of bone–vascular calcification interactions and could be a predictor of the grade of vascular calcification. A recent study [58] demonstrated that coronary arterial calcification (CAC) is significantly associated with plasma OPG values in CKD patients. The serum OPG levels *>*757.7 pg/ml in CKD patients were indicator of CAC. These results are compatible with those reported in our previous study [59]. The relationship between serum OPG concentrations and CAC is unclear. The functional role of circulating OPG has been found to be modulated by several factors, including the relevant association of different tissue sources and the contribution of various comorbidities. OPG has been reported to have protective effect against vascular calcium deposition in experimental models [60]. Interestingly, higher OPG concentrations have been shown in patients with vascular injury, indicating that an elevated OPG concentration may be attribute to a compensatory self-

to the mechanism of the accelerated extraskeletal calcinosis.

8 Updates in Hemodialysis

uncarboxylated MGP level which is related to vascular calcification [56].

defense mechanism that stimulates vascular calcification [61].

Several types of noninvasive methods are useful for screening of the detection of vascular calcification: plain X-rays for visible calcification of the aorta and peripheral arteries; twodimensional ultrasound for detecting calcification of the carotid arteries and femoral arteries; and echocardiography for the evaluation of valvular calcification; and computer tomography (CT) is considered to be the gold standard for quantification of coronary artery and aorta calcification.

Electron-beam CT (EBCT) and multislice CT (MSCT) are relatively sensitive methods for quantitative assessment of vascular calcification, such as CAC, which utilize an electrocardio‐ graphic trigger capable of the evaluation of the heart in diastolic phase, thereby prohibiting moving artifacts [62]. These methods can be usually used to assess the presence of vascular calcifications, the evaluation of longitudinal vascular calcification, and the effect of various treatments on vascular calcification [63]. EBCT is not available in every hospital, although most hospitals have MSCT equipment and, with software applications to enable gated imaging, the new MSCT can evaluate vascular calcification. However, there have been conflicting reports concerning the relationship between the grade of CAC estimated by EBCT and the prevalence of cardiovascular events in ESRD patients [64, 65]. The conflicting results could be confirmed by the evidence that the arterial calcification score evaluated by MSCT is a combination of both medial and intimal calcification, and the finding that is a limitation of the CT-based assessment. MSCT can be used to evaluate aortic calcification [66, 67]. Conventional CT could be used to estimate noncoronary vascular calcification, such as aortic calcification. The area of the aortic circumference that is calcified can be estimated as an aortic calcification index (ACI). It is likely that conventional CT is relatively inexpensive and applicable for screening of vascular calcification. A previous study [72] utilized the conventional CT to estimate aortic calcification in diabetic HD patients. The ACI could not be applicable to evaluate the medial/intimal calcification.

Plain lateral-abdominal X-ray is an inexpensive method for detecting the presence of vascular calcification in CKD patients, but it is semiquantitative, and longitudinal alterations of vascular calcification may not be confirmed. Lateral abdominal X-ray could be utilized as an alternative to CT [69]. The presence of vascular calcification observed on plain X-rays may give some information concerning the pattern of the arterial wall calcification. Kauppila et al. [70] showed the application of lateral lumbar X-rays to confirm the pattern of aortic calcification, in the area responsible to the part of the first to the fourth lumbar vertebrae. This semiquantitative method is a more applicable and less expensive technique for showing arterial calcification and could be utilized for cardiovascular risk management.

We have shown a simple method to study the grade of aortic arch calcification (AoAC) using plain chest X-ray in HD patients [71]. AoAC score (AoACS) was evaluated as a percentage of the proportion of calcified aortic arch, and the mean AoACS was 5.0% ± 4.5% ranging from 0% to 15%. Older age and longer dialysis duration were significant factors in the patients with AoAC. The grade of AoAC was significantly associated with the AoAC volume measured by MSCT. We suggest that screening HD patients for AoAC is a cost-effective method to find patients at the highest risk of cardiovascular diseases and of identifying therapy by inhibiting vascular calcification.
