Effect of rosuvastatin and sevelamer on the progression of coronary artery calcification in chronic kidney disease: a pilot study.

INTRODUCTION: Coronary artery calcification (CAC) is highly prevalent among chronic kidney disease (CKD) patients and its strong association with mortality has been recognized early in the course of CKD. The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients. METHODS: An open-label, randomized and controlled pilot study was conducted including 117 CKD patients (62% men, 56.9 ± 11.2 years, eGFR 36 ± 16.5 ml/min). Patients were randomly assigned to rosuvastatin (n = 38; 10 mg/day), to sevelamer hydrochloride (n = 38; 2,400 mg/day) and to control (n = 41) groups. CAC (by multislice computed tomography) and biochemical analyses were performed at baseline and after 24 months. RESULTS: At baseline, CAC was observed in 55%, 58% and 61% of patients in the rosuvastatin, sevelamer hydrochloride and control groups, respectively (p = 0.87). Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups. Low density lipoprotein cholesterol (LDL-c) was higher and decreased significantly in the rosuvastatin group (p < 0.01). The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC (drug effect p = 0.85; time-effect p < 0.001; interaction p = 0.76). CONCLUSIONS: Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients.

BACKGROUND: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. METHODS: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 ± 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. RESULTS: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. CONCLUSIONS: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

Prospective evaluation of waist circumference and visceral adipose tissue in patients with chronic kidney disease.

BACKGROUND: Waist circumference (WC), a simple anthropometric measure, is associated with visceral adipose tissue (VAT) in cross-sectional studies, and thus has been used as a surrogate marker for VAT. However, associations between changes over time in WC and VAT have not been studied in chronic kidney disease (CKD) patients. METHODS: This prospective study included 87 nondialysis-dependent CKD patients (54 males, 56.2 +/- 10.4 years, BMI 27.3 +/- 5.1, GFR 35.9 +/- 14.6 ml/min/1.73 m(2)). VAT area was measured by computed tomography (CT) and WC was measured at the umbilicus level at baseline and after 12 months. RESULTS: Changes in WC correlated significantly but weakly with changes in VAT (r = 0.26, p = 0.016), likely due to a substantially smaller change in WC compared to changes in VAT. This was also reflected by a kappa coefficient of 0.26, i.e. indicative of poor agreement between WC and CT measurements in regards to quantification of changes in VAT. Likewise, the receiver operating characteristic curve analysis identified WC as poor predictor of changes in VAT (area under the curve = 0.62). CONCLUSION: Anthropometric measurement of WC is poorly correlated with changes in VAT measured by CT in nondialysis-dependent CKD patients. Therefore, caution should be taken when using WC as a surrogate marker of VAT changes in this population.

Intima-media thickness is associated with inflammation and traditional cardiovascular risk factors in non-dialysis-dependent patients with chronic kidney disease.

BACKGROUND: Mortality due to cardiovascular causes is high in chronic kidney disease (CKD). Intima-media thickness (IMT) and inflammation are early atherosclerosis markers, although data are lacking about their association in the CKD non-dialysis-dependent (CKD-NDD) population. The aim of the present study was to evaluate the association between IMT, inflammation and other cardiovascular risk factors in such patients. METHODS: CKD-NDD patients (n = 122) were subjected to measurements of carotid IMT and inflammatory marker levels in a cross-sectional study. RESULTS: Mean patient age was 55.2 +/- 11.3 years (61.5% males). Median C-reactive protein (CRP) was 0.28 mg/dl (0.03-14.2). The median interleukin (IL)-6 count was 4.75 pg/ml (0.7-243), the mean adiponectin was 27.8 +/- 7.3 ng/ml and the mean IMT was 0.61 +/- 0.19 mm. Four (3.3%) patients had IMT above the normal range. IMT was higher in males (p < 0.001), patients with estimated glomerular filtration rate <60 ml/min (p = 0.030), inflammation (p = 0.005) and higher IL-6 levels (p = 0.023). IMT was correlated with age (R = 0.538; p < 0.001), waist circumference (R = 0.235; p = 0.016), CRP (R = 0.191; p = 0.035) and systolic blood pressure (R = 0.181; p = 0.048). In a multiple regression analysis, the independent determinants of IMT were age (beta = 0.512; p < 0.001) and CRP levels (beta = 0.159; p = 0.041). CONCLUSION: The present study demonstrated that although the IMT values were within the normal range, there was a clear association of IMT with age, as well as with inflammation in an asymptomatic CKD-NDD population.

Waist circumference and visceral fat in CKD: a cross-sectional study.

BACKGROUND: In the general population, waist circumference was noted to be a reliable predictor of visceral fat. In addition, increased waist circumference was strongly associated with risk factors for cardiovascular disease. In patients with chronic kidney disease (CKD), the association of waist circumference with visceral fat was never tested. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 122 patients with CKD not yet on dialysis therapy (75 men; diabetes mellitus, 30%; age, 55.3 +/- 11.3 years; body mass index, 27.1 +/- 5.2 kg/m(2); estimated glomerular filtration rate, 35.4 +/- 15.2 mL/min/1.73 m(2)) were studied. PREDICTOR: Waist circumference. OUTCOMES & MEASUREMENTS: Anthropometry, abdominal visceral fat measured by means of computed tomography, and cardiovascular disease risk factors. RESULTS: Waist circumference strongly correlated with visceral fat (r = 0.75 for men, r = 0.81 for women; P < 0.01). kappa Statistic was 0.56, indicating relatively good agreement between methods. Body mass index showed a lower correlation coefficient (r = 0.68 for men, r = 0.76 for women; P < 0.01) and poor agreement (0.36) with visceral fat in comparison to waist circumference. In men, waist circumference and visceral fat similarly correlated with high-density lipoprotein cholesterol level, triacylglycerol level, and Homeostasis Model Assessment Index (P < 0.05). In women, waist circumference correlated with age, C-reactive protein level, and Homeostasis Model Assessment Index, whereas visceral fat also correlated with low-density lipoprotein cholesterol and triacylglycerol levels (P < 0.05). LIMITATIONS: Findings are restricted to patients with CKD not yet on dialysis therapy from a single center. CONCLUSIONS: Waist circumference was strongly associated with visceral fat in patients with CKD. Associations between waist circumference and cardiovascular disease risk factors were similar to those observed for visceral fat, particularly in men. These findings suggest that waist circumference may be a simple and inexpensive tool to be used in epidemiological studies.

Hepatitis C among predialysis patients: prevalence and characteristics in a large cohort of patients.

BACKGROUND: The factors associated with hepatitis C virus (HCV) infection in predialysis patients need to be better investigated. The aims of this study were to evaluate the prevalence, risk factors, clinical, biochemical and virological characteristics of chronic HCV infection in predialysis patients. METHODS: Anti-HCV antibodies were determined in a large cohort of predialysis patients. Epidemiological and laboratorial characteristics of HCV infection were evaluated in predialysis patients and this group was matched to a control group consisting of predialysis patients without viral infection (1:3) and compared in terms of risk factors and alanine aminotransferase (ALT) levels. Logistic regression analysis was applied to identify variables independently associated with chronic HCV infection. RESULTS: A total of 1,041 patients (61% males) with a mean age of 61 +/- 15 years and mean creatinine clearance of 36 +/- 18 ml/min were included. Forty-one (3.9%) patients were anti-HCV positive and, of these, 39 (95%) presented viremia. Predialysis patients with HCV more frequently showed a history of blood transfusion before 1992 (66.7 vs. 10.3%; p < 0.001) and major surgeries (53.8 vs. 17.1%; p < 0.001), a higher proportion of undetermined etiology of kidney disease (43.6 vs. 17.1%; p = 0.001), and higher ALT levels (1.3 vs. 0.4 xULN; p < 0.001). History of blood transfusion before 1992 (p < 0.001; OR: 19), intravenous drug abuse (p = 0.002; OR: 69) and ALT levels (p < 0.001; OR: 50) were the variables that were independently associated with chronic HCV infection. The accuracy of ALT in detecting HCV infection was 92%. The most prevalent HCV genotype was 1b (48.7%) and 56.5% of patients presented high HCV viral load. CONCLUSION: Chronic HCV infection among predialysis patients is related to increased parenteral exposure. Elevated ALT levels suggest the need for HCV screening as part of the predialysis care since ALT seems to be a good marker of this infection.

Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients?

BACKGROUND: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. AIMS: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. METHODS: Thirty-nine predialysis patients with chronic HCV infection were compared to HCV-infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. RESULTS: Predialysis patients were older (57 +/- 10 vs. 45 +/- 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). CONCLUSION: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group.

Pericardial fat is associated with coronary artery calcification in non-dialysis dependent chronic kidney disease patients.

Pericardial fat (PF) a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9 ± 11.0 years, 64.1% males, 95.1% hypertensives, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8 ± 18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. The association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score > 0) was present in 59.2% patients. Those presenting CAC were on average 10 years older, had a higher proportion of male gender (78.7% vs. 42.9%, p < 0.001), and had higher values of waist circumference (95.9 ± 10.7 vs. 90.2 ± 13.2 cm, p = 0.02), PF volumes (224.8 ± 107.6 vs. 139.1 ± 85.0 cm3, p<0.01) and AVF areas (109.2 ± 81.5 vs. 70.2 ± 62.9 cm2, p = 0.01). In the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03-3.43 per standard deviation). PF remained associated with CAC even with additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00-3.42, p = 0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients.

Impact of cardiovascular calcification in nondialyzed patients after 24 months of follow-up.

BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is highly prevalent among patients with chronic kidney disease (CKD), and it has been described as a strong predictor of mortality in the dialysis population. Because there is a lack of information regarding cardiovascular calcification and clinical outcomes in the earlier stages of the disease, we aimed to evaluate the impact of CAC on cardiovascular events, hospitalization, and mortality in nondialyzed patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective study including 117 nondialyzed patients with CKD (age, 57 +/- 11.2 years; 61% male; 23% diabetics; creatinine clearance, 36.6 +/- 17.8 ml/min per 1.73 m(2)). CAC was quantified by multislice computed tomography. The occurrence of cardiovascular events, hospitalization, and death was recorded over 24 months. RESULTS: CAC >10 Agatston units (AU) was observed in 48% of the patients [334 (108 to 858.5) AU; median (interquartiles)], and calcification score >or=400 AU was found in 21% [873 (436-2500) AU]. During the follow-up, the occurrence of 15 cardiovascular events, 19 hospitalizations, and 4 deaths was registered. The presence of CAC >10 AU was associated with shorter hospitalization event-free time and lower survival. CAC >or=400 AU was additionally associated with shorter cardiovascular event-free time. Adjusting for age and diabetes, CAC >or=400 AU was independently associated with the occurrence of hospitalization and cardiovascular events. CONCLUSIONS: Cardiovascular events, hospitalization, and mortality were associated with the presence of CAC in nondialyzed patients with CKD. Severe CAC was a predictor of cardiovascular events and hospitalization in these patients.

Pulse wave velocity--a useful tool for cardiovascular surveillance in pre-dialysis patients.

BACKGROUND: Cardiovascular mortality is high among patients with chronic kidney disease. Pulse wave velocity (PWV) is a simple method used for arterial distensibility evaluation. Few data are available concerning PWV in pre-dialysis patients. The aim of this study was to evaluate the association between PWV and cardiovascular disease in pre-dialysis. METHODS: One hundred and four patients were submitted to PWV analysis, coronary artery calcium (CAC) determination with a multi-slice CT scan of the coronary arteries, echocardiogram and a carotid intima-media thickness (IMT) evaluation, with a high resolution ultrasound. The demographic characteristics and laboratory tests results were studied. RESULTS: The mean age of those studied was 54.4 +/- 11.5 years, 60% were males and the mean creatinine clearance was 40 ml/min/1.73 m(2). The mean PWV was 12.2 +/- 3.4 m/s and it was significantly higher in males, diabetics, those with creatinine clearance <60 ml/min and proteinuria > or =1 g/24 h. PWV was correlated with systolic blood pressure, age, triglycerides, total cholesterol and 24 h proteinuria. In the multiple regression analysis, PWV was significantly associated with diabetes, age, systolic blood pressure and cholesterol. Fifty-eight patients (56%) presented coronary calcification and PWV correlated with coronary calcium score (R = 0.48; P < 0.001) and calcium volume (R = 0.50; P < 0.001). Moreover, PWV was higher in patients with coronary calcification (13.4 +/- 3.6 m/s vs 10.7 +/- 2.4 m/s; P < 0.001). The mean left ventricular mass index (LVMI) was 106 +/- 31 g/m(2) and 24% of patients had left ventricular hypertrophy, while 19 (18.3%) patients had left ventricular dysfunction. PVW was correlated with LVMI (R = 0.25; P = 0.01) while no association could be seen between PWV and the ejection fraction or left ventricular dysfunction. A correlation between the IMT and PWV was observed (R = 0.27; P = 0.005). In addition, those with a thicker IMT had a higher PWV (13.2 +/- 3.4 m/s vs 11. 2 +/- 3.2 m/s; P = 0.003). CONCLUSION: PWV is associated with cardiovascular disease in pre-dialysis patients and can be a useful tool to identify patients with increased cardiovascular risk.