Vascular Calcification Score Research Articles

MTHFRC677T Polymorphism as a Risk Factor for Vascular Calcification in Chronic Hemodialysis Patients

Polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T is one of the suggested risk factors for atherosclerosis. However, few studies have reported on the relationship between MTHFR C677T polymorphism and vascular calcification (VC) in chronic hemodialysis patients. We investigated the relationship between the MTHFR C677T polymorphism and VC in 152 chronic hemodialysis patients. Patients with a TT genotype exhibited significantly higher VC scores than patients expressing CC and CT (P = 0.002). The prevalence of peripheral vascular disease increased with the incidence of MTHFR C677T mutations for all patients, and the incidence of cerebrovascular accidents also increased with the presence of mutations for young patients (≤ 60 yr) (P < 0.05). Patients with CT and TT genotypes had adjusted odds ratios for VC of 1.39 and 1.58, respectively (P < 0.05). In summary, these data suggest that the MTHFR C677T polymorphism affects the degree of VC in chronic hemodialysis patients.

Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5

Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. Vascular calcification is highly prevalent in this population and is an independent predictor of cardiovascular mortality. Vascular calcification in uraemic patients is known to be an active and regulated process subject to the action of many promoting and inhibitory factors. The role of vitamin D in this process remains controversial. We evaluated the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and vascular calcification evaluated by plain X-ray images, in predialysis patients with CKD stages 4 and 5. We performed a cross-sectional study with 210 CKD patients stages 4 and 5 managed at our predialysis unit. Patients were 63.5 ± 13 years of age, 60.5% males, 64.8% diabetics and 47.1% with a history of CVD. Plain X-ray images of pelvis, hands and lateral lumbar spine from all subjects were studied for calculation of semiquantitative vascular calcification scores as described by Adragao and Kauppila. We found a high prevalence of vascular calcification in our population. Adragao scores revealed only 47 patients (22.4%) without vascular calcification and 120 (57.1%) with scores higher than 3. Kauppila scores revealed only 29 patients (13.8%) without aortic calcifications and 114 patients (54.3%) with scores higher than 7. Higher vascular calcification scores were related to older age, diabetes, history of CVD and lower levels of 25(OH)D. Only 18.5% of patients had adequate levels of 25(OH)D (> 30 ng/mL), 53.7% of them had insufficient levels (15-30 ng/mL) and 27.8% had deficient levels (< 15 ng/mL). Multivariate analysis showed that age, diabetes and CVD were directly associated and 25(OH)D levels were inversely associated with vascular calcifications. Our results show an independent and negative association between serum levels of 25(OH)D and vascular calcification. Further and larger prospective studies are needed to clarify the possible role of vitamin D deficiency in the development of vascular calcification in CKD patients.

Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them?

Vascular calcifications (VCs) and renal osteodystrophy (ROD) are frequently seen together and represent the major causes of morbidity and mortality in hemodialysis (HD) patients. Some studies suggest a pathogenic link between them, but there is no consensus as yet regarding this issue. The main objective of our study was to establish whether there is any relation between VCs and ROD in our HD patients. We evaluated the prevalence of VCs and ROD and the relationship between VCs and some clinical and biochemical characteristics of HD patients. We examined radiological signs of VCs and ROD on hands and pelvis bone radiographs in 81 chronic HD patients, and we calculated a VC score on this basis. We found a significant relation between radiological signs of ROD and those of VC (P=0.019). The patients with ROD had a higher mean VC score (P=0.02). By linear regression, the VC score correlated directly with serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and CaxP product and inversely with serum albumin. The logistic regression model revealed that ROD, male gender and treatment with calcium salts were predictive of VCs development. There were no associations between VCs and age, HD vintage, diabetes, dialysate Ca concentration, vitamin D treatment, spKt/V, URR and C-reactive protein (CRP) levels. There seems to be a pathogenetic link between bone and artery diseases in chronic HD patients. Both VCs and ROD have a high prevalence. ROD, male gender and treatment with calcium salts are risk factors for VCs.

Factors associated with aortic stiffness and its change over time in peritoneal dialysis patients

An increase in aortic stiffness, as reflected by an increase in pulse wave velocity (PWV), is an important predictor of cardiovascular mortality in dialysis patients. Decreased serum concentration of calcification inhibitor, such as fetuin-A, is inversely related to mortality in haemodialysis patients. Our aim is to investigate the factors associated with aortic stiffness and its change over time in peritoneal dialysis (PD) patients. As a prospective observational study, we analysed 67 PD patients, aged 50 ± 14 years (mean ± SD) and with dialysis duration of 26 (5-58) months (median, interquartile range). At baseline, age, mean arterial pressure (MAP), left ventricular mass (LVM) index, diabetes, serum albumin, calcium (Ca), phosphorus (P) and intact parathyroid hormone (iPTH), uric acid, total bilirubin, high-sensitivity C-reactive protein (hsCRP), fetuin-A, and residual renal function were included in association analysis with aortic stiffness represented by heart-to-femoral PWV (hfPWV). We also evaluated simple vascular calcification score (SVCS) with plain radiograph of the pelvis and both hands. PWV was measured both at baseline and at 1 year. Change of aortic stiffness was determined by △PWV (difference between 1-year PWV and baseline PWV). Time-averaged concentrations were used to evaluate the relation between biologic markers and changes of aortic stiffness. hfPWV was 1022 ± 276 cm/s at baseline, and hfPWV determined at 1 year was 1069 ± 317 cm/s. Mean serum fetuin-A concentration was 0.34 ± 0.08 g/L. At baseline, aortic PWV positively correlated with age, smoking status, diabetes, MAP, total cholesterol and LDL cholesterol. On the other hand, aortic PWV inversely correlated with fetuin-A, log PTH, haemoglobin and albumin. In a multiple regression model, association of serum fetuin-A (β = -0.329, P = 0.003) with aortic PWV remained significant, along with age (β = 0.512, P < 0.001), MAP (β = 0.215, P = 0.047) and log PTH (β = -0.269, P = 0.025). At follow-up, △MAP (β = 0.500, P < 0.001) and time-averaged TG (aTG) (β = 0.259 P = 0.019) were determinants of △PWV. For our PD patients, serum fetuin-A was an independent determinant of aortic stiffness, as well as age, MAP and log PTH. Although 1 year is not sufficient to observe the change of aortic stiffness, some patients exhibited >15% increase of PWV during this period. △MAP and aTG were factors affecting the change of PWV. Follow-up over a longer period is necessary to elucidate factors that determine changes of aortic stiffness over time from PD patients.

Association of AHSG Gene Polymorphisms and Aortic Stiffness in Peritoneal Dialysis Patients

Background/Aims: Fetuin-A is a negative acute-phase reactant and extraosseous calcification inhibitor. Decreased serum concentration of fetuin-A is independently related to all-cause and cardiovascular mortality in dialysis patients. Our aim is to investigate the association between the genetic polymorphism of α₂-Heremans-Schmid-glycoprotein (AHSG) encoding fetuin-A and its serum concentration, vascular calcification, and aortic stiffness in peritoneal dialysis (PD) patients. Method: A total of six single nucleotide polymorphisms (SNPs) in the AHSG gene were genotyped and evaluated for association with serum fetuin-A level, quantitative measures of vascular calcification and aortic stiffness represented by heart-to-femoral pulse wave velocity (hfPWV). Results: Five SNPs in the AHSG gene were nominally associated with the serum fetuin-A level in our PD patients. In haplotype analyses, there were haplotypes positively (H1; AGCA, H2; CC) and inversely (H1; TTCG, H2; TT) related with the serum fetuin-A level. The serum fetuin-A level inversely and independently correlated with hfPWV. Moreover, the serum fetuin-A concentration was a determinant for the simple vascular calcification score (SVCS), which subsequently was associated with hfPWV. Conclusions: Our study showed an association between AHSG polymorphism and its serum concentration, and also revealed an association of the serum fetuin-A level with SVCS and aortic stiffness in PD patients.

Vascular calcification score on plain radiographs of the feet as a predictor of peripheral arterial disease in patients with chronic kidney disease

The incidence of lower extremity amputation is increasing in patients with chronic kidney disease (CKD), but symptoms of peripheral arterial disease (PAD) in patients with CKD are uncommon. The aim of the current study was to assess the value of the vascular calcification (VC) score on plain radiographs of the feet for the prediction of PAD in patients with CKD. We recruited 102 patients with CKD (24 pre-dialysis, 58 hemodialysis [HD], and 20 peritoneal dialysis [PD]). We defined the VC score on the plain radiographs of the feet as follows: score 0, no calcification; score 1, the length of the VC is <5 cm in a single foot or <2 cm in both feet; and score 2, the length of the VC is >5 cm in a single foot or >2 cm in both feet. We evaluated the atherosclerotic calcified plaques of the femoral or popliteal artery with Doppler ultrasonography and compared it with the VC score. Patients with high VC scores showed more atherosclerotic calcified plaques in the femoral or popliteal artery (P < 0.01). The prevalence of PAD in patients with CKD was closely related with the VC score (P < 0.01). PAD was associated with diabetes, a higher hsCRP, and a lower total cholesterol level (P < 0.01). The VC score was a significant predictor of the presence of PAD (odds ratio: 6.66, P < 0.001). Asymptomatic CKD patients, including those on HD and PD, may have PAD and routine testing by plain radiographs of the feet followed by Doppler ultrasonography are of pivotal significance, especially if the patients are diabetic.

Relationship of sRANKL Level and Vascular Calcification Score to Cardiovascular Events in Maintenance Hemodialysis Patients

Background: Vascular calcification and cardiovascular events are common in hemodialysis patients. Receptor activator of nuclear factor-κB ligand (RANKL) plays an important role in vascular calcification and bone remodeling. This study investigates the effects of soluble RANKL (sRANKL) on cardiovascular events in hemodialysis patients. Methods: Serum sRANKL levels of 47 patients were tested by ELISA. Vascular calcification was radiographically measured and patients were followed up for 2 years. Results: After 2 years, 10 (36.6%) patients had experienced cardiovascular events. Seventy-five percent (6/9) of mortality was due to cardiovascular disease. Patients experiencing cardiovascular events showed significantly higher vascular calcification scores (VCS) (3.20 ± 2.74 vs. 1.19 ± 1.60; t = 2.999; p < 0.05). Multivariate regression analysis showed that serum sRANKL levels, vascular calcification scores and phosphorus were independent determinants of cardiovascular events. Conclusion: Serum sRANKL levels and VCS are independent risk factors, and hemodialysis patients with low serum sRANKL levels have a risk of cardiovascular events.

Sevelamer versus calcium-based phosphate binders in chronic kidney disease: what should we conclude from the evidence to date?

Calcium-based phosphate binders have traditionally been considered standard first-line treatment for control of hyperphosphataemia in chronic kidney disease (CKD). However, several cross-sectional studies have observed that prescribed calcium intake from phosphate binders is dose-dependently associated with the degree of vascular calcification in CKD patients [1,2]. Other studies have demonstrated an association between vascular calcification scores and an increased risk of cardiovascular disease [3– 5]. Although there is presently no proof that interventions that reduce the surrogate outcome of vascular calcification lead to reduced cardiovascular events in CKD patients, the K/DOQI guidelines have recommended that the ‘total dose of elemental calcium provided by the calcium-based phosphate binders should not exceed 1500 mg/day (opinion), and the total intake of elemental calcium (including dietary calcium) should not exceed 2000 mg/day (opinion)’ [6]. If these guidelines are followed, there is likely to be a substantial shift in clinical practice away from the use of calciumbased phosphate binders to non-calcium-based phosphate binders, such as sevelamer, which are considerably more expensive. This raises the important question of just how good is the evidence that sevelamer therapy results in superior patient-level outcomes (i.e. ‘hard’ clinical end-points) compared with calcium-based phosphate binder therapy? To date, there has only been one randomized controlled trial (RCT) of sevelamer versus calcium-based binders, which has been adequately powered for mortality. The Dialysis Clinical Outcomes Revisited (DCOR) study involved 75 centres and 2103 haemodialysis patients randomly allocated to receive either sevelamer or a calcium-based phosphate binder for a mean follow-up period of ∼20 months [7]. Sevelamer-treated patients experienced comparable allcause mortality [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.79–1.10] and cardiovascular mortality (HR 0.93, 95% CI 0.74–1.17) to patients receiving calciumbased binders. Based on a significant interaction between the pre-specified variable of age and treatment effect (P = 0.02), a subsequent age-stratified analysis demonstrated that sevelamer was associated with a reduction in mortality in patients aged 65 years or older (HR 0.77, 0.61– 0.96). However, these results were limited by the fact that the authors did not correct their interaction assessments for multiple comparisons, which would have yielded a nonsignificant result. A subsequent intention-to-treat analysis of the DCOR study using pre-planned secondary analyses and Centers for Medicare & Medicaid Services data demonstrated no significant differences in overall or cardiovascular mortality and no significant interaction between age and treatment effect [8]. A meta-analysis of RCTs, including the DCOR study, observed that sevelamer treatment was associated with similar all-cause mortality (risk difference −2%, 95% CI −6%– 2%; 5 RCTs and 2429 participants) and cardiovascular mortality (risk difference −1%, 95% CI −4%–2%; 3 RCTs and 2102 participants) compared with calcium-based phosphate binder therapy [9]. The authors concluded that there was ‘no convincing evidence that sevelamer improves clinically relevant outcomes in ESRD patients’ and that ‘recommendations for the routine use of sevelamer in dialysis patients are not supported by current data.’ In this issue of Nephrology Dialysis and Transplantation, Jamal et al. report the results of an updated systematic review of the effects of calcium-based versus non-calciumbased phosphate binders on mortality in CKD patients [10]. Eight RCTs of sevelamer versus calcium-based binders were selected. The study was sponsored by Genzyme (manufacturers of sevelamer) and one of the authors declared a potential conflict of interest with Genzyme. Similar to the findings of the previous meta-analysis, Jamal et al. reported no significant differences between patients treated with sevelamer or calcium-based phosphate binders with respect to coronary artery calcification (WMD −76.35, 95% CI −158.25–5.55; 5 RCTs and 469 participants), cardiovascular events [relative risk (RR) 0.85, 95% CI 0.35– 2.03; two RCTs and 153 participants] or all-cause mortality (RR 0.68, 95% CI 0.41–1.11; eight RCTs and 2873 participants). In spite of the non-significant differences between the groups, the authors concluded that there were ‘trends’ towards decreased all-cause mortality, cardiovascular mortality and coronary artery calcification associated with noncalcium-based phosphate binders and that future studies are needed to conduct ‘research on the mechanism by which non-calcium-based phosphate binders reduce mortality or

High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients

Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival. All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles. The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality. This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.

Relationship between vascular calcification, arterial stiffness and bone mineral density in a cross‐sectional study of prevalent Australian haemodialysis patients

Cardiovascular disease in dialysis patients is associated with increased vascular calcification (VC) and arterial stiffness, both inversely correlated with bone mineral density (BMD). Few studies have correlated VC in the dialysis population with measurements of BMD and arterial compliance. We report cross-sectional data on 45 haemodialysis (HD) patients assessing the prevalence of VC and its associations. Patients had computed tomography scans through abdominal aorta and superficial femoral arteries (SFA) to determine VC, pulse wave velocity (PWV) using SphygmoCor device measuring arterial stiffness, and dual-energy X-ray absorptiometry (DXA) to determine BMD. Patients, 64% male, 38% diabetic, had median age 58 years. Mean PWV was 8.7 +/- 3.5 m/s and median aortic VC score 488.1 +/- 298 Hounsfield units, with 91% having aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with length of HD (P = 0.03) and diabetes (P = 0.06). Increasing PWV was positively associated with age (P = 0.001), diabetes (P = 0.05) and VC (aortic P = 0.08, SFA P = 0.01). In multivariate regression analysis, length of HD and diabetes were significantly associated with aortic VC, whereas age and diabetes were associated with SFA VC and PWV. Mean lumbar spine and femoral neck T-scores on DXA were 0.14 and -1.66 respectively. Increased VC and reduced arterial compliance, both closely related, are common in Australian HD patients. Both are associated with diabetes and increasing age, and greater aortic VC is seen with longer duration of dialysis.

25-Hydroxyvitamin D3, arterial calcifications and cardiovascular risk markers in haemodialysis patients

Decreased vitamin D serum levels have been recently related to arterial stiffening and vascular calcifications in haemodialysis (HD) patients, but the pathophysiology of this association is not yet clear. The aim of this study was to evaluate the relationship between vascular calcifications, cardiovascular risk factors [including brain natriuretic peptide (BNP), pulse pressure (PP) and left ventricular mass index] and 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] serum levels. We performed a cross-sectional study with 223 prevalent HD patients, 48% females, 27% diabetics, with the mean age of 62.7 +/- 15.3 years and the mean HD time of 42.9 +/- 39.3 months. Forty-seven percent of the patients were taking active forms of vitamin D. Serum levels of [25(OH)D3] were low (21.6 +/- 12.2 ng/mL) and negatively correlated with age (r = -0.31, P < 0.001), diabetes mellitus (DM) (r = -0.20, P = 0.004), C-reactive protein (r = -0.25, P < 0.001), log(10) BNP (r = -0.22, P = 0.002), PP > 65 mmHg (r = -0.21, P = 0.003) and vascular calcifications (r = -0.26, P < 0.001). Levels of [25(OH)D3] were positively correlated with [1,25(OH)(2)D3] (r = 0.25, P < 0.001) and albumin (r = 0.23, P = 0.001). On multivariate analysis, levels of [25(OH)D3] were independently associated with DM (P < 0.001), lower albumin levels (P = 0.003), higher BNP values (P = 0.005), PP > 65 mmHg (P = 0.006) and a higher vascular calcification score (>or= 3) (P = 0.002). These results suggest that lower levels of [25(OH)D3] are a cardiovascular risk marker in HD patients, since they are strongly associated with higher BNP levels, increased PP and with the presence of vascular calcifications. The exact role of [25(OH)D3] deficiency on cardiovascular morbi-mortality needs to be clarified in large randomized controlled trials.

Bone Mineral Density, Vascular Calcifications, and Arterial Stiffness in Peritoneal Dialysis Patients

The objective of this study was to evaluate the correlation of bone mineral density (BMD), evaluated by DXA, with vascular calcifications, arterial stiffness, and vascular disease in patients on peritoneal dialysis. Vascular calcifications were evaluated by vascular calcification score on plain x ray, and arterial stiffness was measured by pulse wave velocity using the Complior device (Artech Medical, Pantin, France). Adjusting for multiple factors, lower BMD at the femoral neck, but not at the lumbar spine, was associated with higher pulse wave velocity (p = 0.037), higher vascular calcification score (p = 0.013), and peripheral artery disease (p = 0.006). These data reinforce the hypothesis of the existence of a link between bone disease and cardiovascular disease in dialysis patients.

A plain X-ray vascular calcification score is associated with arterial stiffness and mortality in dialysis patients

Vascular calcifications are highly prevalent in dialysis patients and are associated with arterial stiffness and mortality. The use of simple and inexpensive methods to evaluate arterial stiffness and vascular calcifications is desired. The objective of this study was to evaluate the relationship of a simple vascular calcification score (SVCS) with pulse wave velocity (PWV) and pulse pressure (PP) and to evaluate their association with all-cause mortality. 101 haemodialysis patients (71 men; 19% diabetic) were evaluated. At baseline, arterial stiffness was measured by PP and by PWV with Complior. SVCS was evaluated in plain X-ray of pelvis and hands. During a 43-month observational period, 31 patients died. By Kaplan-Meier analysis, SVCS >3 (P = 0.001), PP > 70 mmHg (P = 0.001) and PWV > 10.5 m/s (P < 0.001) were found to be associated with lower cumulative survival. Adjusting for multiple variables, association with mortality was maintained for SVCS >3 (HR = 3.308, P = 0.032) and PP > 70 mmHg (HR = 3.227, P = 0.031) in all patients and for PWV > 10.5 m/s (HR = 2.981, P = 0.047) in non-diabetic patients. Age (P < 0.001), systolic pressure (P = 0.004) and SVCS > 3 (P = 0.032) were associated with PWV. Diabetes (P = 0.031), calcium carbonate dose (P = 0.009) and SVCS > 3 (P = 0.012) were associated with PP. Higher SVCS, PWV and PP were associated with higher mortality in this population. SVCS was associated with arterial stiffness. Simple and inexpensive methods such as PP or SVCS may be used to detect mortality risk and to provide important information that may be relevant for guiding therapeutic intervention in dialysis patients.

Vitamin D Deficiency and Associated Factors in Hemodialysis Patients

Vitamin D deficiency is prevalent in the general elderly population, and is related to an increased risk of osteoporosis, fractures, and cardiovascular calcification. Only limited data and no guidelines are available on vitamin D deficiency in hemodialysis patients. We aimed to assess the frequency of, and factors associated with, 25(OH) vitamin D deficiency in hemodialysis patients in a French dialysis center. In March 2006, we studied all prevalent hemodialysis patients who had not received native vitamin D supplements in the recent past. According to the Kidney Disease Outcomes and Quality Initiative guidelines, patients were assigned to the following 3 groups: group 1, with a sufficient vitamin D serum level (>75 nmol/L); group 2, with an insufficient level (25 to 75 nmol/L); and group 3, with severe deficiency (<25 nmol/L). Patients' characteristics and biochemical findings were compared between patients of groups 1 and 3. Of 253 patients, 11% patients were in group 1; 47% were in group 2; and 42% were in group 3. The proportions of female and diabetes patients were 42% and 34%, respectively. The mean (+/- SD) age of all patients was 66.7 +/- 14 years, and the mean duration of dialysis was 62 +/- 74 months, with a mean schedule of 3 x 6.5 hours and administration of a 1.5 mmol/L calcium dialysate. Concomitant treatment included alfacalcidol (66% of patients) and sevelamer (34% of patients) as a standard phosphate binder. Group 3 patients had a lower dialysis vintage (53 +/- 66 vs. 73 +/- 85 months, P < .05), a higher number of diabetes patients (45% vs. 21%, P < .05), a higher number of female patients (53% vs. 28%, P < .05), and a higher level of intact parathyroid hormone (260 +/- 227 vs. 213 +/- 153 pg/mL, P < .05) than group 1 patients. No relationship was found between vitamin D storage levels and bone markers, serum calcium, phosphorus, albumin, body mass index, normalized protein catabolic rate, radiologic vascular calcification score, and hip bone mineral density. In multivariate logistic regression analyses, no factors were significantly associated with vitamin D deficiency. Calcidiol deficiency was highly prevalent in a French dialysis population. The associated factors mainly included female sex, diabetes, shorter dialysis duration, and higher intact parathyroid hormone level. Although there are no guidelines for the therapy of patients with chronic kidney disease at stage 5, the usefulness of vitamin D supplementation may be assessed by considering its potential direct action, the need for providing fuel for renal and extrarenal calcitriol production in particular, and the numerous potential favorable effects on health.

Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease

Vascular calcification (VC) and arterial stiffness are major contributors to cardiovascular (CV) disease in chronic kidney disease (CKD). Both are independent predictors of CV mortality and are inversely correlated with bone mineral density (BMD). Few studies have addressed the extent of VC in the pre-dialysis CKD population, with associated measurements of BMD and arterial compliance. We report cross-sectional data on 48 patients with CKD (GFR 17-55 ml/min) assessing the prevalence of VC and its associations. All patients had computed tomography (CT) scans through abdominal aorta and superficial femoral arteries (SFAs) to determine VC, pulse wave velocity (PWV) using SphygmoCor device (AtCor PWV Inc., Westmead, Australia) measuring arterial stiffness, and dual-energy X-ray absorptiometry (DEXA) scans to determine BMD, as well as serum markers of renal function and mineral metabolism. Patients, 71% male, 54% diabetic, had a median age 64.5 years. Mean estimated GFR was 35.1 +/- 10 ml/min. Mean PWV was 10.0 +/- 4.5 m/s and mean aortic VC score was 421.5 +/- 244 Hounsfield units, with 90% of subjects having some aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with age (r 0.50, P < 0.001), triglycerides (r 0.47, P = 0.002) and PWV (r 0.33, P = 0.03). There was also greater VC with declining renal function (r -0.28, P = 0.05). There was no significant association between VC and serum markers of mineral metabolism, however phosphate and Ca x P correlated positively with PWV (r 0.35, P = 0.02, r 0.36, P = 0.02, respectively). There was also a positive association between PWV and triglycerides (P = 0.008), and a trend towards greater PWV with increasing age (P = 0.09). In multivariate regression analysis only increasing age and triglyceride levels were significantly associated with aortic VC and PWV. Mean spine and femoral T-scores on DEXA were 0.48 and -1.31 respectively, with 13% of subjects having femoral T-score <-2.5 (osteoporotic range). SFA VC inversely correlated with femoral T-scores (r -0.43, P = 0.004); however, there was a positive (likely false) association between spine T-scores and aortic VC (r 0.37, P = 0.01), related to the limitation of vertebral DEXA in CKD. There is a high prevalence of VC in pre-dialysis CKD patients, worse with increasing age, triglycerides and reducing renal function. Correlation exists between VC and PWV and determination of one or both may be useful for CKD patient CV risk assessment. Femoral BMD is inversely associated with SFA VC, but measurement of vertebral BMD by DEXA is unreliable in CKD patients with aortic VC.

Measurement of vascular calcification using CT fistulograms

Vascular calcification (VC), precipitated by calcium and phosphate imbalance, is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD). Electron-beam computed tomography (EBCT) quantitatively assesses coronary artery calcification (CAC), with VC scores predictive of atherosclerosis and cardiac events in the general and CKD population. EBCT is not readily available but spiral CT can also provide quantitative assessment of the extent of VC. CT fistulograms can be used as initial investigation for arterio-venous fistula (AVF) problems in haemodialysis (HD). The images obtained include thoracic aorta, brachio-cephalic, subclavian and common carotid arteries which allow assessment of the extent of VC in these vessels. No study to date has combined the CT fistulogram with concurrent determination of VC. We hypothesize that a single investigation for AVF management may also provide information on VC. We retrospectively analysed CT fistulograms on 28 HD patients determining VC scores (in Hounsfield units) in AVF, subclavian and carotid arteries and aorta. We correlated these scores with patient demographics, serum markers of mineral metabolism (time averaged for the period 6 months prior to CT) and calcium-based phosphate binders. Patients (60.7% male) had a median age of 59 years and 46.4% were diabetic. The mean duration of dialysis was 17.5 months. CT fistulograms showed predominantly aortic (75% of patients) and subclavian (75%) calcifications, with only 21.4% having carotid VC and minimal VC at the level of AVF. Median VC scores were 619.8 (0-1481.4) for aorta and 521.7 (0-1139.6) for subclavian (scores of >400 indicate severe atherosclerotic disease), but there was no significant correlation with serum markers or duration of HD. Increasing age correlated significantly with greater VC in aortic (R = 0.53, P = 0.003) and subclavian (R = 0.40, P = 0.03) vessels, as well as with the number of VC sites involved. CAC was present in most patients (89.3%) but CAC scores were not able to be determined because of cardiac movement. Concurrent determination of the degree of calcification in certain vessels may be possible from CT studies assessing AVF structure. VC scores provided by CT fistulograms could contribute to HD patient CVD risk assessment but studies with larger patient numbers are required to determine their relevance.

Association of pelvic arterial calcification with arteriovenous thigh graft failure in haemodialysis patients.

Arterial calcification is a common problem in patients with chronic kidney disease, and has been associated with adverse clinical outcomes. The goal of the present study was to evaluate whether pelvic artery calcifications are associated with technical failure of arteriovenous thigh grafts in haemodialysis patients. From 1 January 1999 to 30 June 2002, thigh grafts were placed in 54 haemodialysis patients who had exhausted all options for permanent vascular access in the upper extremities. Perioperative computed tomography (CT) of the abdomen and pelvis was obtained in 32 of the patients for diagnostic purposes unrelated to vascular access planning. Two radiologists, who were blinded to the graft outcomes, scored the vascular calcifications on CT of the distal aorta, common iliac, external iliac and common femoral arteries on a semi-quantitative 5-point scale. The association between technical graft failure (inability to complete the anastomosis) and the vascular calcification score was analysed. There was a high inter-observer agreement in scoring vascular calcification (kappa = 0.801). Among 26 patients with absent or mild pelvic arterial calcifications (grade 1-2) on CT, none (0%) experienced technical graft failure. In contrast, three of six patients (50%) with moderate to severe calcification (grade 3-5) had technical graft failures (P = 0.004 by Fisher's exact test). The cumulative 1 year graft patency was lower in the group with grade 3-5 calcification (33 vs 81%, P = 0.09). The two groups were similar in age, gender, race, diabetes, duration of dialysis, serum calcium, serum phosphorus and serum parathyroid hormone. There is a strong association between pelvic artery calcifications and technical failure of thigh grafts. The presence of moderate to severe vascular calcification is predictive of poor cumulative 1 year graft patency.

A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients

Cardiovascular morbidity and mortality are highly prevalent in haemodialysis (HD) patients and have been recently associated with vascular calcifications. The objective of our study was to assess the value of a simple vascular calcification score for the prediction of cardiovascular death, cardiovascular hospitalizations and fatal and non-fatal cardiovascular events in HD patients, and to correlate this score with cardiovascular disease and with other known predictors of vascular disease. In this observational, prospective study 123 chronic HD patients (75 males and 48 females; 20% diabetic) were included, who were on low-flux HD treatment for 46.6+/-52 months (mean+/-SD). We set up a simple vascular calcification score based on plain radiographic films of pelvis and hands. Brachial pulse pressure and mean arterial pressure (MAP) were measured and cardiovascular events and hospitalization episodes were assessed. During an observational period of 37 months there were 17 cardiovascular deaths; 28 patients needed cardiovascular hospitalizations and 32 patients suffered fatal and non-fatal cardiovascular events. Coronary artery disease was diagnosed in 43 patients (35%), peripheral arterial disease in 33 patients (26.8%), cerebrovascular disease in 16 patients (13%) and vascular disease (coronary artery disease or peripheral arterial disease or cerebral vascular disease) in 61 patients (49.6%). By binary logistic regression, diabetes (P = 0.01), male sex (P<0.001), age (P = 0.02), HD duration (P = 0.02) and MAP (P = 0.03) were independently associated with a vascular score > or =3. This score > or =3 was independently associated with coronary artery disease (P = 0.008), peripheral arterial disease (P<0.001) and vascular disease (P = 0.001). Patients with a vascular calcification score > or =3 had a 3.9-fold higher risk of cardiovascular mortality (P = 0.03), a 2.8-fold higher risk of cardiovascular hospitalizations (P = 0.02) and a 2.3-fold higher risk of fatal or non-fatal cardiovascular events (P = 0.04). The present vascular calcification scoring represents a simple tool for the assessment of cardiovascular risk related with vascular calcifications in chronic HD patients.