Aortic Calcification Index Research Articles

Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients

Vascular calcification has detrimental consequences on chronic kidney disease (CKD) patients, yet its pathogenesis is not fully understood. Fibroblast growth factor-23 (FGF-23) is involved in the regulation of mineral metabolism which may in turn affect vascular calcification. Data on the relationship between FGF-23 and peripheral vascular calcification, using conventional radiographs, are conflicting, and less is known about its relation to aortic calcification. We conducted this study to investigate the relationship between FGF-23 and aortic calcification in a standard haemodialysis setting. The study included 65 haemodialysis patients (46 prevalent and 19 incident) on a three times 4-h dialysis schedule as well as 15 controls. Those with diabetes, oral anticoagulation or parathyroidectomy were excluded. Intact FGF-23, parathormone, lipids, calcium and phosphorus were measured. Aortic calcification index (ACI) was assessed by a non-contrast computerized tomography (CT) of the abdominal aorta. FGF-23 levels were higher among haemodialysis patients (4681.3 +/- 3906.1 pg/mL) compared to controls (98.2 +/- 51.9 pg/mL), P = 0.005. ACI was higher in haemodialysis patients (14.1 +/- 12) than controls (3.2 +/- 3.6), P = 0.009. FGF-23 (P < 0.0001) and systolic blood pressure (BP) (P < 0.0001) were independently related to ACI in stepwise multiple regression analysis of pooled analysis of haemodialysis patients, R(2) = 0.476; in subgroup analysis, the independent factors relating to ACI among prevalent dialysis patients were systolic BP (P < 0.0001), FGF-23 (P = 0.002) and age (P = 0.012), R(2)=0.48; whereas in incident patients, only FGF-23 was associated with ACI (P = 0.007), R(2) = 0.37. In haemodialysis patients, FGF-23 and ACI were significantly increased, and FGF-23 was independently associated with aortic calcification.

Assessment and significance of abdominal aortic calcification in chronic kidney disease

Abdominal aortic calcification is a common complication and a predictor of cardiovascular mortality in dialysis patients. However, abdominal aortic calcification in pre-dialysis chronic kidney disease (CKD) is poorly understood. A cohort study of 101 adult Japanese patients (mean age 66.6 +/- 11.3 years old) with pre-dialysis CKD (18, 29 and 54 in stages 3, 4 and 5, respectively) was performed. At entry, a non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI). Clinical characteristics and laboratory variables were also assessed. The patients were followed for a mean period of 48 +/- 12 months. Among the subjects, 82% had abdominal aortic calcification (50, 83 and 91% for CKD stages 3, 4 and 5, respectively), and the median ACI was 16.7% (8.5, 20.0 and 21.4%, respectively). Multivariate logistic regression analyses identified older age, presence of diabetes and decreased estimated glomerular filtration rate (e-GFR) as independent predictors of the presence (ACI > 0%) and extent (ACI >or= 20%) of aortic calcification. Multivariate Cox proportional hazards analysis identified ACI >or= 20% and diabetes as independent predictors for de novo cardiovascular events in CKD stages 4 and 5. Decreased GFR may be associated with the presence and extent of abdominal aortic calcification, and a high level of calcification may be associated with de novo cardiovascular events in pre-dialysis CKD, suggesting that elucidation of the mechanism through which CKD contributes to vascular calcification may lead to an improved prognosis in patients with pre-dialysis CKD.

Improved Assessment of Aortic Calcification in Japanese Patients Undergoing Maintenance Hemodialysis

Vascular calcification is a feature of arteriosclerosis and in hemodialysis (HD) patients it may be severe, even at a relatively young age, and is closely related to the overall prognosis. We used the aortic calcification area index (ACAI), derived from the aortic calcification index (ACI), to evaluate and analyze the risk factors for abdominal aortic calcification in HD patients. Subjects comprised 137 patients on maintenance HD. ACAI was measured on abdominal plain computed tomography: 10 slices of the abdominal aorta were obtained at 1-cm intervals from the bifurcation of the common iliac artery and the area of the aortic cross-section and calcification was measured using image software. The calcification area was divided by the cross-sectional area and expressed as a percentage (%). The mean value for the 10 slices was also calculated. Patients were divided into 2 groups according to ACAI being lower or higher than the mean value and the risk factors in each group were compared by multivariate analysis. Results Group comparison showed significant differences in age, systolic blood pressure, serum calcium, and lipoprotein(a). On multiple regression analysis, age, systolic blood pressure, and serum calcium were independent risk factors. On logistic regression analysis, age, duration of dialysis, systolic blood pressure, and serum calcium were independent risk factors. Risk factors for abdominal aortic calcification in HD patients include age, systolic blood pressure, and serum calcium, according to ACAI evaluation. The ACAI was accurate and useful for evaluating abdominal calcification.

Clinical assessment of atherosclerotic parameters and cardiac function in chronic hemodialysis patients

Atherosclerosis is evaluated by carotid mean intima-media thickness (mean IMT), pulse wave velocity (PWV), and the aortic calcification index (ACI). We have attempted to examine if these atherosclerotic parameters are associated with each other and which parameters are closely related to cardiac function in chronic HD patients. The mean IMT, PWV and ACI were examined in 69 maintenance HD patients using carotid ultrasonography, a blood volume plethysmographic apparatus and abdominal CT, respectively. Echocardiographic studies were also performed for measuring left ventricular (LV) geometry. Serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, albumin, C-reactive protein (CRP), calcium and phosphate were measured. The mean IMT correlated positively with ACI (r = 0.461, P < 0.0001) and tended to be correlated with PWV, but did not reach statistical significance. The PWV value correlated positively with ACI (r = 0.494, P <or= 0.0001). The mean IMT correlated positively with the LV mass index (r = 0.273, P = 0.0228), and fractional shortening (FS) correlated negatively with PWV value (r = -0.293, P = 0.0141) and ACI score (r = -0.289, P = 0.0158). Multivariate analyses indicated that the LV mass index was independently associated with mean IMT (P = 0.0231) as well as systolic blood pressure (P < 0.0001), pulse pressure (P < 0.0001) and hemoglobin (P = 0.016), and FS is independently associated with ACI (P = 0.0162) as well as PWV (P = 0.0144) and CRP (P = 0.0375). Atherosclerosis and reduced LV function are associated with increased vascular calcification and arterial stiffness in chronic HD patients.

Raloxifene ameliorates progressive bone loss in postmenopausal dialysis patients with controlled parathyroid hormone levels

Postmenopausal women undergoing chronic hemodialysis are at risk of uremic bone disease and postmenopausal osteoporosis. There are few reports discussing the effects of raloxifene hydrochloride on chronic hemodialysis patients. We investigated whether differences in the effects of raloxifene on bone mineral density (BMD) are dependent on the level of intact parathyroid hormone (iPTH). 47 postmenopausal hemodialysis patients with osteoporosis were divided into two groups, i.e. Group A, with treatment, and Group B, without treatment by raloxifene hydrochloride (60 mg/day, three times per week) for 1 year. We evaluated the changes in BMD at the distal one-third of the radial bone and aortic calcification index (ACI) by plain abdominal computerized tomography. Furthermore, we compared the BMD and ACI results for patients with similar iPTH levels within each group. After 1 year of raloxifene treatment, patients with iPTH levels of < 250 pg/ml in Group A showed significantly less BMD deterioration than similar patients in Group B (A: -0.31 +/- 1.7% vs. B: -3.71 +/- 0.7%, p = 0.04). However, raloxifene showed no difference in patients with iPTH levels of > or = 250 pg/ml in the two groups (A: -3.49 +/- 0.7% vs. B: -6.10 +/- 1.9%, p = 0.09). Among the patients with iPTH levels of < 250 pg/ml, changes in the ACI values were 1.30 +/- 0.3% for Group A and 1.67 +/- 1.0% for Group B. Among the patients with iPTH levels of (3) 250 pg/ml, the ACI values were 2.58 +/- 0.7% for Group A and 3.01 +/- 1.2% for Group B. Raloxifene treatment was useful for the prevention of BMD deterioration in postmenopausal dialysis patients with controlled iPTH levels.

Associations between vascular calcification, arterial stiffness and bone mineral density in chronic hemodialysis patients

The aim of our study was to examine the associations between vascular calcification, arterial stiffness and bone mineral density (BMD) in chronic hemodialysis (HD) patients. The study subjects were 83 (70 men and 13 women) HD patients. All patients had computed tomography (CT) to determine aortic calcification index (ACI), pulse wave velocity (PWV) using a volume-plethysmographic apparatus, and BMD estimated by digital image processing (DIP). Patients, 84.3% male, 38.6% diabetic, had a mean age of 59.3 +/- 11.2 years. In univariate linear regression analysis, ACI correlated positively with age (r = 0.586, P < 0.0001), dialysis vintage (r = 0.47, P = 0.002), pulse pressure (r = 0.311, P = 0.004), C-reactive protein (CRP) (r = 0.226, P = 0.0397) and PWV (r = 0.422, P < 0.0001). There was no significant association between ACI and serum markers of mineral metabolism. There was also a positive association between PWV and systolic blood pressure (P = 0.0004) or pulse pressure (P < 0.0001), and a trend towards greater PWV with increasing age (r = 0.494). In multivariate regression analysis only increasing age, pulse pressure, serum levels of albumin and CRP were significantly associated with ACI and PWV. Mean BMD on DIP was 2.7 +/- 0.4 mmAL. ACI was inversely correlated with BMD (r = -0.234, P = 0.0331). Vascular calcification is closely associated with arterial stiffness in HD patients. BMD is inversely correlated with ACI, suggesting that measurement of hand BMD by DIP is a useful tool for assessment of renal bone disease in these patients.

Elevated Osteoprotegerin Levels Predict Cardiovascular Events in New Hemodialysis Patients

Background: Patients on hemodialysis (HD) frequently experience cardiovascular events associated with vascular calcification. We investigated the involvement of osteoprotegerin (OPG), an inhibitor of vascular calcification, in the incidence of cardiovascular events and mortality among new HD patients. Methods: We conducted a prospective cohort study of the association of serum OPG levels with morbidity and mortality in subjects who became new HD patients between June 2000 and May 2006. Results: A total of 99 patients (age 58.9 ± 14.6 years, 65 male, 34 female) were prospectively followed up for 41.5 ± 20.2 months. During this period, 27 patients developed cardiovascular events and 12 died of causes related to cardiovascular disease. When divided into 2 groups according to OPG levels, the high OPG group showed a higher prevalence of cardiovascular morbidity and mortality compared with the low OPG group. Cox’s proportional hazards analysis associated the new onset of cardiovascular events with the high OPG group (HR 2.88, 95% CI 1.09–7.62, p = 0.033). Furthermore, the high OPG group at the start of HD was significantly associated with older age, male gender and a high aortic calcification index. Conclusions: Elevated levels of serum OPG in new HD patients may predict subsequent cardiovascular events.

Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis

Fibroblast growth factor (FGF) 23 is a circulating factor that regulates phosphate (P) metabolism. Since higher P levels are associated with vascular calcification, we examined the role of serum FGF-23 levels in P metabolism and vascular calcification in hemodialysis (HD) patients with and without diabetes mellitus (DM). Chronic HD patients with DM (n = 39) and without DM (n = 50) were enrolled. Serum samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Abdominal computed tomography (CT) scan was performed, and the aortic calcification index (ACI) was determined by one examiner, blinded to the patient characteristics. Measurements of bone mineral density (BMD) were performed at the time of ACI estimation. Log plasma FGF-23 levels were higher in non-DM (3.74 +/- 0.71 pg/ml) than in DM (3.35 +/- 0.74 pg/ml) patients. The log FGF-23 correlated positively with serum creatinine (r = 0.424, P < 0.0001), albumin (r = 0.225, P = 0.0337), Ca (r = 0.392, P = 0.0001), P (r = 0.735, P < 0.0001), and Ca x P product (r = 0.780, P < 0.0001). There were negative correlations between log FGF-23 and age (r = -0.208, P = 0.0497), glucose (r = -0.231, P = 0.0294), and CRP (r = -0.222, P = 0.0359). Multiple regression analyses were performed to explore the correlations between plasma FGF-23 and other factors associated with vascular calcification in all HD patients. Independent variables were selected based on the results of univariate analyses. The significant factors associated with FGF-23 in HD patients were age, serum levels of creatinine, albumin, glucose, Ca, P, and Ca x P product. Plasma FGF levels did not correlate significantly with either ACI or BMD in these patients. Our findings indicate that the plasma FGF-23 level is associated with calcium-phosphate metabolism disorders, but not with aortic calcification, in both non-DM and DM patients on chronic HD. In addition, plasma FGF-23 is associated with serum levels of creatinine and albumin. Therefore, the plasma FGF-23 level may provide a reliable marker for Ca and P imbalance and nutritional status in HD patients.

Effects of Sevelamer on the Progression of Vascular Calcification in Patients on Chronic Haemodialysis

Background/Aim: Vascular calcification is thought to be associated with a high cardiovascular mortality rate in patients with end-stage renal disease. Control of hyperphosphataemia is important for the treatment of the vascular calcification. The aim of the present study was to evaluate the effects of sevelamer hydrochloride on the progression of aortic calcification in haemodialysis (HD) patients. Methods: 42 HD patients were studied in this study and divided into two groups (sevelamer vs. calcium). Sevelamer was added and titrated up to achieve serum P control for 6 months. The estimations of aortic calcification index (ACI) by abdominal computed tomography scans were performed twice in each patient. We compared the changes in serum calcium, phosphorus, intact parathyroid hormone, and lipids in two groups. Results: Serum phosphorus levels decreased significantly from 6.7 ± 0.7 to 6.2 ± 0.5 mg/dl with no changes in serum intact parathyroid hormone levels in the sevelamer group (p < 0.01), and increased from 6.5 ± 1.0 to 6.7 ± 1.1 mg/dl in the calcium group (p < 0.05). Serum calcium levels did not change in the sevelamer group and calcium group. The serum levels of total cholesterol decreased significantly from 158.5 ± 20.7 to 146.2 ± 24.1 mg/dl (p = 0.024) and the low-density lipoprotein cholesterol level from 65.3 ± 14.4 to 54.7 ± 11.6 mg/dl (p = 0.014) in the sevelamer group. Serum C-reactive protein decreased significantly from 0.14 ± 0.13 to 0.08 ± 0.11 mg/dl in the sevelamer group (p = 0.038) and significantly increased (0.18 ± 0.09 vs. 0.22 ± 0.12 mg/dl) in the calcium group (p = 0.042). The mean changes in ACI (ΔACI) were 3.6 ± 1.5% in the sevelamer group and 8.2 ± 3.1% in the calcium group. Conclusions: Sevelamer allows a better serum phosphorus control compared with calcium-based phosphate binder and suppresses the progression of aortic calcification in HD patients.

Radial Augmentation Index is Related to Cardiovascular Risk in Hemodialysis Patients

Cardiovascular accidents related to atherosclerosis are the leading cause of death among hemodialysis patients, which makes continuous monitoring of their cardiovascular status crucial. Recently, a handy device for monitoring the augmentation index (AIx) in the radial artery was introduced in Japan, enabling the use of the AIx in addition to pulse wave velocity (PWV) in the management of hemodialysis patients. In this study the AIx, PWV, abdominal aortic calcification index (ACI), and left ventricular mass index (LVMI) were serially assessed in 108 hemodialysis patients. The radial AIx was monitored using a newly introduced tonometer (HEM-9010AI), and the interrelationships among the measured parameters and their contributions to the risk of cardiovascular accidents were evaluated. The radial AIx was significantly higher in hemodialysis patients than in healthy subjects (N = 50) and was well correlated with risk markers such as LVMI (r = 0.30, P = 0.019) and ACI (r = 0.38, P < 0.001), but not with PWV. Multiregression analysis showed that radial AIx was also significantly associated with LVMI, ACI and blood pressure; PWV was associated with other parameters such as age, blood pressure, and ACI. The AIx and ACI were both significantly increased in patients with cardiovascular complications. Although PWV was strongly increased in the hemodialysis patients, it failed to discriminate between these subgroups of high-risk patients. The radial AIx is closely associated with aortic calcification, cardiac hypertrophy, and a history of cardiovascular accidents in hemodialysis patients, and could be a useful marker for management of these patients.

Carotid intima media thickness and aortic calcification index closely relate to cerebro‐ and cardiovascular disorders in hemodialysis patients

Atherosclerosis can be evaluated by carotid intima media thickness (IMT), the aortic calcification index (ACI), and pulse wave velocity (PWV). We investigated which test was most closely related to cerebro- and cardiovascular disorders (CCVD) in hemodialysis patients. Maximum IMT (max-IMT), ACI, and PWV were examined in 110 hemodialysis patients, using carotid ultrasonography, abdominal CT and a blood pressure pulse wave instrument, respectively. Blood hemoglobin A1c (HbA1c), serum total cholesterol, high density lipoprotein cholesterol, triglyceride, total protein, albumin, high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor alpha were measured. The patients were divided into two groups; with and without CCVD and the degree of atherosclerosis was evaluated in each group. Compared to the CCVD (-) group, the CCVD (+) group showed significantly higher percentages of males and diabetic patients, higher levels of HbA1c (5.14 vs 4.83%) and hs-CRP (0.320 vs 0.167 mg/dL), an older age group (64.5 vs 57.5 years), a greater max-IMT (2.05 vs 1.19 mm), and a higher ACI (71.8 vs 41.0%); and significantly lower diastolic blood pressure (82.8 vs 89.2 mmHg). Multiple logistic regression analysis showed that the factors influencing the development of CCVD were age (odds ratio: 1.092), ACI (odds ratio: 1.025), and max-IMT (odds ratio: 2.006). However, PWV did not significantly relate to CCVD. In hemodialysis patients, the ACI and max-IMT were significantly associated with CCVD, but the association of PWV was weak. A prospective cohort study is warranted to determine the risk factors for CCVD in hemodialysis patients.

Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis

Vascular calcification is an independent determinant of cardiovascular events in maintenance haemodialysis (HD) patients. It is not known whether acute changes of the serum calcium concentration before and after HD (DeltaCa) are associated with the development of aortic calcification. We enrolled 71 patients dialysed with a dialysate with 3.0 mEq/l calcium and determined their aortic calcification index (ACI) by abdominal computed tomography twice at an interval of 3 years. To identify the factors contributing to the rate of progression of aortic calcification, we analysed the average values for clinical and laboratory data obtained between the first and second evaluations of ACI. The second ACI (mean+/-SD: 80.2+/-63.9) was significantly greater than the first ACI (61.0+/-61.0) after an interval of 35.8+/-4.2 months. The annualized change of ACI (DeltaACI/year) was significantly and directly associated with the DeltaCa and C-reactive protein (CRP) (both P<0.001, P for trend). Stepwise multivariate regression analysis revealed that DeltaACI/year was positively and independently associated with CRP, presence of diabetes mellitus and DeltaCa, but negatively associated with a premenopausal status in women. Similarly, DeltaCa was positively and independently associated with DeltaACI/year and the ultrafiltration rate, but was negatively associated with pre-HD Ca. The increase of serum calcium after HD was related to the rate of progression of aortic calcification. Excess calcium is transferred into patients on HD when using a dialysate of 3.0 mEq/l calcium. This may be a risk factor for the development of vascular calcification.

Association of Homocysteine and Asymmetric Dimethylarginine With Atherosclerosis and Cardiovascular Events in Maintenance Hemodialysis Patients

Homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) recently were recognized as potential risk factors for atherosclerosis in the general population, and the metabolism of each of these substances seems to be closely related. This study investigates the association between these substances and whether elevated serum Hcy and ADMA levels are related to high risk for atherosclerosis and cardiovascular events in maintenance hemodialysis (HD) patients. A study was made of 197 HD patients (132 men, 65 women; mean age, 56.9 +/- 8.6 years) for the correlation between plasma total Hcy (tHcy) and ADMA concentrations and the association of these substances with atherosclerotic indices of cervical intima-media thickness, plaque diameter, aortic calcification index, and aortic elongation. Cardiovascular events were followed up for 5 years in these patients. Mean plasma tHcy (37.3 +/- 25.8 micromol/L) and ADMA (0.77 +/- 0.16 micromol/L) levels were significantly greater in HD patients than in healthy subjects. Plasma tHcy level did not correlate with plasma ADMA level (r = -0.1; P = not significant). Although ADMA level was associated significantly with atherosclerotic indices from a simple regression analysis, this association was less from multiple regression analysis. When patients were classified into 3 groups according to ADMA level, cardiovascular events during 5 years were significantly greater in the group with the highest ADMA levels than in the other groups, confirmed by using a Cox proportional hazard model. However, no association was found between tHcy levels and atherosclerotic indices or cardiovascular events. ADMA level emerged as a potential risk factor for cardiovascular events that might be mediated in part by atherosclerosis in HD patients. Conversely, neither high nor low plasma tHcy levels were associated with atherosclerotic indices and cardiovascular events. This result for our HD patients does not fulfill the terms of traditional epidemiology and paradoxical reverse epidemiology of Hcy.

Serum Level of Macrophage Colony-Stimulating Factor and Atherosclerosis in Hemodialysis Patients

Background/Aims: Atherosclerosis and its related complications are the leading causes of death in the hemodialysis (HD) population. Aortic calcification index (ACI), intima-media thickness (IMT) in common carotid arteries, and electrocardiogram (ECG) are atherosclerotic parameters that are available in usual clinical outpatient settings. Macrophage colony-stimulating factor (MCSF) and monocyte chemoattractant protein-1 (MCP-1) play important roles in atherosclerosis. Methods: We performed a cross-sectional study of 133 outpatients on maintenance HD in a single HD outpatient center. We measured serum levels of MCSF and MCP-1, determined the ACI using computed tomography scan and the IMT using high-sensitivity ultrasound B-mode imaging, and performed ECGs. Results: Stepwise multivariate regression analysis revealed that the MCSF level correlated with age-adjusted mean and maximum IMT (F = 10.811, p = 0.001, and F = 6.784, p = 0.010, respectively) as well as with the diastolic blood pressure. Age and MCSF level (F = 4.866, p = 0.029) were independently related to an increased ACI. High-sensitivity C-reactive protein (hsCRP) was not related to IMT and ACI. The hsCRP level (χ² = 5.002, p = 0.025) correlated with ECG changes followed by MCSF (χ² = 3.940, p = 0.047). MCP-1 was not related to the above atherosclerotic parameters. Conclusion: A head-to-head comparison between MCSF and hsCRP revealed that MCSF was more closely associated with IMT and ACI in HD patients.

Aortic calcification in haemodialysis patients with diabetes mellitus

Certain metabolic disorders, such as hyperphosphatemia induce vascular calcification in haemodialysis patients; it is unclear, however, whether these disorders contribute to aortic calcification in diabetic haemodialysis patients. This study examined the risk factors of aortic calcification in a large number of haemodialysis patients, and compared risk factors between diabetic and non-diabetic patients. The subjects were 667 patients on maintenance haemodialysis: 184 with type 2 diabetes and 483 without. Aortic calcification was measured semi-quantitatively using a plain computed tomography image of the abdominal aorta, and an aortic calcification index (ACI) was calculated. The ACI of the diabetic subjects was significantly higher than that of those without diabetes (57.3+/-22.1 vs 44.8+/-28.3%, P < 0.0001), although the dialysis vintage of the former was significantly shorter (P < 0.001). Multiple regression analyses showed that diabetes was a significant independent risk factor for increased ACI. Multiple regression analyses, performed separately in diabetics and non-diabetics, revealed that advanced age, higher systolic blood pressure, smoking and longer haemodialysis vintage were common independent risk factors significantly associated with increased ACI in both patient groups (R2 = 0.296, P < 0.0001 for non-diabetics; R2 = 0.193, P < 0.0001 for diabetics). Higher serum phosphate concentration was not significantly associated with increased ACI in diabetic patients (P = 0.429), although it was a significant independent factor in non-diabetic patients (beta = 0.150, P < 0.0005). Aortic calcification in diabetic haemodialysis patients is more advanced, compared with non-diabetic patients, even with short haemodialysis vintage. Since disorders of mineral metabolism are not significantly associated with aortic calcification in diabetic haemodialysis patients, aortic calcification in these patients could be affected by metabolic abnormalities associated with the diabetic state per se, independent of other confounding factors; and aortic calcification may be advanced even before haemodialysis induction.

Management of Calcium, Phosphorus and Bone Metabolism in Dialysis Patients Using Sevelamer Hydrochloride and Vitamin D Therapy

Abnormalities of mineral metabolism, including those of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) in patients on maintenance hemodialysis induce severe bone involvement, which manifests as renal osteodystrophy. Recently, vascular calcification caused by abnormal mineral metabolism has been attracting attention because cardiovascular diseases (CVD) are a major cause of death in hemodialysis patients. Since 2000, the treatment standard for overt secondary hyperparathyroidism (SHPT) in our facilities has shifted from conventional or pulse therapy with oral vitamin D3 (VitD) to intravenous pulse therapy with maxacalcitriol or calcitriol. After selecting the criterion of overt SHPT as intact-PTH>500 pg/mL, the proportion of overt SHPT cases among all hemodialysis patients decreased from 12% at the start of intravenous pulse treatment to 6.4% after 4 years' treatment. However, the number of patients who had an interruption to pulse treatment because of hypercalcemia and/or hyperphosphatemia was high and it became a bottleneck for the continuation of the therapy. The major cause of hypercalcemia is considered to be Ca load derived from oral calcium carbonate. In Japan, sevelamer hydrochrolide (SH), which does not contain Ca, has been available commercially since 2003 and potentially should enable a reduction in the incidence of overt SHPT during long-term intravenous treatment when combined with careful adjustment of the dose of VitD and strict monitoring of Ca and P level concentrations. In this study, we found that the proportion of patients who satisfy the recommended serum concentrations of Ca and P reported by K/DOQI guideline was low irrespective of the serum concentration of intact-PTH. The aortic calcification index was high in the patient group with lower intact-PTH level concentration, probably because of reduced Ca and P buffering ability associated with reduced bone turnover. We consider that VitD treatment with SH might give better control of the intact-PTH level concentration within the range recommended by the K/DOQI guideline.

Predictive value of serum macrophage colony-stimulating factor for development of aortic calcification in haemodialysis patients: a 6 year longitudinal study

Accelerated atherosclerosis is a major complication in patients on haemodialysis (HD). Macrophage colony-stimulating factor (MCSF) is a representative regulator of activation of monocytes and macrophages, and plays important roles in the development of atherosclerosis in HD patients. However, the long-term predictive value of the serum MCSF level for the development of aortic calcification under HD conditions has not been reported. Serum MCSF level was measured in 40 HD patients. The aortic calcification index (ACI) was also calculated on computed tomography once each year for 6 years. Predictive value was examined by logistic regression analysis. At baseline, there was a significant correlation between serum MCSF and ACI (r = 0.43, P<0.01). A significant increase in ACI was first noted at 4 years post-baseline and the increase was maintained thereafter in the high MCSF group. No such changes were noted in the low MCSF group. Univariate analysis identified high levels of calcium x phosphorus product, triglyceride, C-reactive protein (CRP), MCSF and presence of diabetes mellitus as significant predictors for increased ACI at 6 years. However, among these five factors, high levels of CRP and MCSF were the only independent and significant predictors (odds ratio = 24.0, P = 0.03 and odds ratio = 22.8, P = 0.02, respectively). Our results demonstrated that MCSF is associated with the process of atherosclerosis in HD patients. Furthermore, the serum MCSF level is an independent long-term predictor of increased ACI. These results provide useful information for preventive strategies against atherosclerotic disease under HD conditions.

Prognostic Impact of Aortic Calcification Index and Ankle-Arm Blood Pressure Indexin Patients under Hemodialysis

The mortality rate is high in patients receiving hemodialysis (HD), atherosclerotic diseases being the major cause of death. As marker of clinical outcome, a prospective examination of atherosclerotic tests and atherosclerotic risk factors in patients receiving HD was performed. On April 2000, 84 patients receiving HD were followed up until April 2002. At entry to the study, several atherosclerotic tests, including ankle-arm blood pressure index (API), aortic calcification index (ACI), and atherosclerotic risk factors, were performed. In 36 patients with old thrombotic events, 26 had new thrombotic events. Of 48 patients without previous thrombotic events, 15 had new thrombotic events. During 2 years, 41 patients had new thrombotic events and 15 patients died due to thrombotic disorders. The HD durations were significantly longer in non-survivors than survivors and the body mass index was lower in non-survivors than survivors. There was a significant difference in the values of ACI and API between survivors and non-survivors, and between patients with and without thrombotic events. These findings suggest that the ACI and API have a prognostic value because they might predict the occurrence of thrombosis.

Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients.

Osteoprotegerin (OPG) is a glycoprotein that inhibits osteoclast differentiation and activity. OPG-deficient mice develop severe osteoporosis and medial arterial calcification. The expression of OPG is detected in early atherosclerotic lesions in non-uraemic patients. We examined whether serum OPG is associated with aortic calcification in haemodialysis patients. Serum OPG was measured in 102 patients who were undergoing haemodialysis. The aortic calcification index (ACI) was assessed by computed tomography scans. Serum OPG level, measured by enzyme-linked immunosorbent assay, was significantly greater in patients with higher ACI than in those with lower ACI. There was a direct relationship between ACI and serum OPG levels and a positive association between OPG and ACI (r = 0.483, P<0.0001). Multiple regression analyses indicated that serum OPG levels were independently associated with the severity of aortic calcification (P<0.0001). These findings show that serum OPG levels are associated with the extent of vascular calcification, suggesting that OPG may be involved in the development of vascular calcification in haemodialysis patients.

Left Ventricular Hypertrophy Is Associated with Arterial Stiffness and Vascular Calcification in Hemodialysis Patients

Left ventricular hypertrophy (LVH) is the most frequent cardiac abnormality in patients with end-stage renal disease (ESRD). Recent studies have shown that arterial stiffness is associated with mediacalcinosis in these patients. However, whether arterial stiffness and vascular calcification are associated with the LVH in patients with ESRD has not been well established. Forty-nine patients on chronic hemodialysis participated in this study. 1) To better understand the mechanism underlying the increased incidence of LVH, we studied the relation between LVH and each of arterial wall stiffness, aortic calcification, and numerous clinical parameters in 49 patients on chronic hemodialysis. 2) To evaluate the contribution of arterial stiffness and arterial calcification to LVH in hemodialysis patients, we performed the present clinical analysis on 49 patients on chronic hemodialysis. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The left ventricular mass index (LVMI) was estimated by M-mode echocardiography. To understand the mechanism underlying the increased incidence of LVH, we examined the factors contributing to LVMI in these patients. The correlation between each of the study parameters and LVMI as an indicator of LVH was then examined. The LVMI value was correlated positively with PWV (r=0.439, p=0.0014), systolic blood pressure (r=0.421, p=0.0023), and ACI (r=0.467, p=0.0006). A stepwise linear regression analysis showed that PWV, systolic blood pressure, and ACI were independently associated with LVH in our subjects. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients, with vascular calcification being the most important contributor to the development of LVH. Alteration of pulsatile dynamics contributes to an increase in left ventricular load and thus is also related to the LVH in these patients. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients. Vascular calcification, which alters the pulsatile dynamics and thereby contributes to an increase in left ventricular load, is the most important contributor to the development of LVH in patients undergoing hemodialysis.