Thirty-month follow-up of coronary artery calcification in hemodialysis patients: different roles for inflammation and abnormal calcium-phosphorous metabolism?

BACKGROUND: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. Coronary artery calcification (CAC) is considered a marker of atherosclerosis and coronary artery disease (CAD). The CAC progression and factors that influence it were evaluated during a 30-month period. METHODS: Forty HD patients without a history of CAD were enrolled into the study. CAC score was assessed with conventional CT repeated every six months. The circulating factors of phosphorous, calcium, calcium-phosphorous product, intact parathyroid hormone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein-alpha, albumin, high sensitivity C-reactive protein, and fibrinogen were measured monthly. Hypertension and calcium intake during the study period were taken into account as well. RESULTS: At baseline, CAC score was correlated with age and duration of HD therapy. From all evaluated factors, CAC initiation was influenced only by older age and C-reactive protein. CAC, when it was started, was aggravated continuously and was influenced only by elevated serum phosphorous and calcium-phosphorous product. Hypertension, lipid profile, and calcium intake did not affect CAC initiation or progression. CONCLUSIONS: Once CAC progression starts, it is an uninterrupted process. The roles of inflammation and abnormal calcium-phosphorous metabolism in CAC differ. Inflammation is the major factor that contributes in CAC initiation. Elevated serum phosphorous and calcium-phosphorous product accelerates CAC progression.

Aortic stiffness in patients undergoing hemodialysis is positively related to antigen presenting cell-dependent T-lymphocyte reactivity.

BACKGROUND: Aortic stiffness is increased in patients undergoing hemodialysis (HD), and it is associated with an increased cardiovascular mortality. Among others, aortic stiffness has been correlated with serum markers of inflammation, indicating a role of the immune system in its pathogenesis. The aim of this study was to evaluate the impact of antigen-presenting cell-dependent T-lymphocyte reactivity on aortic stiffness in HD patients. PATIENTS AND METHODS: Twenty patients were enrolled in the study. Exclusion criteria were medications or conditions, other than HD, that are known to influence the immune response or aortic stiffness. Antigen-presenting cell-dependent T-lymphocyte reactivity was assessed by cell proliferation of peripheral blood mononuclear cells cultured with or without stimulation with Staphylococcal enterotoxin B (SEB). Cell proliferation was estimated by immunoenzymatic measurement of bromodeoxyuridine uptake. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measurement. RESULTS: Linear regression analysis revealed a strong positive relation between carotid-femoral PWV and antigen-presenting cell-dependent T-lymphocyte reactivity, when SEB at concentrations of 1 ng/mL or 10 ng/mL was used as stimulant. CONCLUSION: The present study confirms that aortic stiffness in HD patients is positively related to antigen-presenting cell-dependent T-lymphocyte reactivity. The greater the ability of the immune system to react to a monocyte-dependent stimulant and, consequently, to provoke an inflammatory response, the greater the stiffness of the aorta. This is in agreement with the observation that aortic stiffness in HD patients is positively related to various serum inflammation markers.

The value of computed tomography-derived coronary artery calcification score in coronary artery disease detection in asymptomatic hemodialysis patients.

BACKGROUND: We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated. METHODS: CAC score was assessed with conventional computed tomography in 40 patients. Thirty patients completed EECG and 25; those with a positive CAC score and/or a positive EECG performed Thallium dipyridamole scintigraphy. Carotid-femoral PWV was assessed in all patients. RESULTS: There was no association among CAC score and EECG or Thallium dipyridamole scintigraphy. In contrast, CAC score was correlated with aortic PWV. CONCLUSION: The previous results question the role of CAC score in the detection of CAD in asymptomatic HD patients. The correlation between CAC score and aortic PWV raises the possibility that CAC score represents more an indicator of coronary artery medial wall calcification than a marker of CAD.

Effect of 1-year oral alpha-tocopherol administration on anticardiolipin antibodies in hemodialysis patients.

BACKGROUND: Anticardiolipin antibodies (ACA) have been related to an increased incidence of thrombotic episodes and atherosclerosis progression. ACA levels are elevated in hemodialysis (HD) patients. Atheroembolic episodes are the major cause of morbidity and mortality in this population. Oxidative stress has been implicated in ACA formation, and it is increased in HD patients. Vitamin E is a known antioxidant factor. In this study, the effects of prolonged oral alpha-tocopherol administration on ACA levels were evaluated. METHODS: Serum anticardiolipin IgG antibodies (ACA-IgG) and IgM antibodies (ACA-IgM) levels were evaluated in 27 stable HD patients and 22 healthy volunteers. Then measurements were performed in the patients' group after oral administration of alpha-tocopherol at a dose of 500 mg/d for a 1-year period. ACA levels were assessed by solid-phase enzyme immunoassay. RESULTS: ACA-IgG levels were higher in HD patients compared with control (13.3 +/- 6.64 GPL/mL vs. 7.727 +/- 18.305 GPL/mL, p < .001). This was not the case for ACA-IgM levels (2.96 +/- 4.18 MPL/mL vs. 1.386 +/- 2.636 MPL/mL, p=.17). alpha-Tocopherol administration resulted in a further increase in ACA-IgG (26.7 +/- 14.7 GPL/mL vs. 13.3 +/- 6.64 GPL/mL, p < .001) and ACA-IgM levels (8.17 +/- 1.95 MPL/mL vs. 2.96 +/- 4.18 MPL/mL, p < .001) in HD patients. CONCLUSIONS: Prolonged oral alpha-tocopherol administration in HD patients increases ACA levels. The mechanism and the clinical significance of this finding need further evaluation.

Impaired T cell proliferation and zeta chain phosphorylation after stimulation with staphylococcal enterotoxin-B in hemodialysis patients.

BACKGROUND: Patients on regular hemodialysis treatment are in an immunodeficiency state. Several studies have shown defective T cell proliferation after stimulation with various agents. Staphylococcal enterotoxin B (SEB) is a MHC-dependent superantigen that triggers proliferation of a large proportion of T cells. T cell activation after stimulation with SEB parallels normal T cell signal transduction. An important and early event in this transduction pathway is the phosphorylation of the zeta chain. In this study, T cell proliferation and zeta chain phosphorylation after stimulation with SEB were evaluated. METHODS: Peripheral blood mononuclear cells (PBMCs) from 24 patients and 14 healthy individuals were isolated and cultured with or without stimulation with SEB (1 ng/ml). Cell proliferation was estimated by immunoenzymatic measurement of bromodeoxyuridine uptake. PBMCs from 8 patients and 6 healthy individuals were isolated and pulsed for 2 min with or without SEB (10 microg/ml). Zeta chain phosphorylation was estimated by immunoprecipitation and immunoblotting with antiphosphotyrosine antibody. RESULTS: Lymphocyte proliferation index after SEB stimulation was lower in hemodialyzed patients. Stimulation of T cells with SEB also resulted in a lower zeta chain phosphorylation in hemodialyzed patients. CONCLUSIONS: Lymphocyte proliferation after MHC-dependent stimulation is impaired in hemodialyzed patients. This proliferation defect is due to impaired zeta chain phosphorylation.