PURPOSE: Cardiovascular diseases are a common cause of mortality in patients with end stage renal disease and are associated with vascular calcification (VC) and arterial stiffness. In addition to high turnover bone disease, there is substantial evidence that low levels of serum intact PTH (iPTH) are associated with vascular calcium deposition. The objective was to evaluate the association of iPTH levels with VC, arterial stiffness, and to identify risk factors contributing to VCs and arterial stiffness. METHODS: One hundred five hemodialysis (HD) patients were divided into three groups according to iPTH levels: A, <150 pg/mL; B, 150< or =and< or =400 pg/mL; and C, >400 pg/mL. The simple vascular calcification score (SVCS) was obtained by X-ray; the brachial ankle-pulse wave velocity (ba-PWV) and the serum fetuin-A level was mesured. RESULTS: Patients in group A were older and had a higher SVCS, a prevalence of diabetes, and an increased arterial stiffness. Severe VCs (SVCS> or =3) were associated with the low iPTH group (iPTH<150)/a higher CRP/a lower diastolic blood pressure (DBP)/diabetes/ increased arterial stiffness/older age and a lower serum fetuin-A level. The log [ba-PWV] had a positive correlation with age, systolic blood pressure (SBP)/DBP/PP/CRP/presence of diabetes and low iPTH and a negative correlation with serum albumin. Based on multivariate analysis, the low iPTH group and diabetes were identified as independent risk factors of severe VC and age/SBP/CRP and diabetes were risk factors for arterial stiffness. CONCLUSION: Low iPTH levels and/or diabetes had a greater risk of developing VCs and age/SBP/CRP/diabetes were associated with increased arterial stiffness in HD patients.
alpha-2-HS-Glycoprotein ; Blood Pressure ; Blood Vessels ; Bone Diseases ; Calcium ; Cardiovascular Diseases ; Humans ; Kidney Failure, Chronic ; Multivariate Analysis ; Parathyroid Hormone ; Prevalence ; Renal Dialysis ; Risk Factors ; Serum Albumin ; Vascular Calcification ; Vascular Stiffness

Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with < 1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. alpha2-HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P < 0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.
Adult ; Alpha-Globulins/metabolism ; Amino Acid Sequence ; Biological Markers/blood ; Blood Proteins/*analysis ; Case-Control Studies ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/blood ; Molecular Sequence Data ; Pre-Eclampsia/*blood/diagnosis ; Pregnancy ; Proteome/*analysis ; Retinol-Binding Proteins, Plasma/metabolism ; alpha-2-HS-Glycoprotein/metabolism

BACKGROUND/AIMS: Osteoprotegerin (OPG) and fetuin-A are vascular calcification regulators that may be related to high cardiovascular (CV) mortality in hemodialysis (HD) patients. We evaluated the relationship between OPG, fetuin-A, and pulse wave velocity (PWV), a marker of vascular stiffness, and determined whether OPG and fetuin-A were independent predictors of CV events in HD patients. METHODS: We conducted a prospective observational study in 97 HD patients. OPG and fetuin-A were measured at baseline and arterial stiffness was evaluated by PWV. All patients were stratified into tertiles according to serum OPG levels. RESULTS: A significant trend was observed across increasing serum OPG concentration tertiles for age, HD duration, systolic blood pressure, cholesterol, triglycerides, and PWV. Multiple linear regression analysis revealed that diabetes (beta = 0.430, p = 0.000) and OPG levels (beta = 0.308, p = 0.003) were independently associated with PWV. The frequency of new CV events was significantly higher in the upper OPG tertiles compared with those in the lower OPG tertiles. In Cox proportional hazards analysis, upper tertiles of OPG levels were significantly associated with CV events (hazard ratio = 4.536, p = 0.011). CONCLUSIONS: Serum OPG, but not fetuin-A, levels were closely associated with increased vascular stiffness, and higher OPG levels may be independent predictors of new CV events in HD patients.
Adult ; Aged ; Biological Markers/blood ; Cardiovascular Diseases/blood/diagnosis/*etiology/mortality/physiopathology ; Female ; Humans ; Kaplan-Meier Estimate ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoprotegerin/*blood ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Pulse Wave Analysis ; *Renal Dialysis/adverse effects/mortality ; Renal Insufficiency, Chronic/complications/diagnosis/mortality/*therapy ; Risk Factors ; Up-Regulation ; *Vascular Stiffness ; alpha-2-HS-Glycoprotein/analysis

BACKGROUND/AIMS: We assessed changes in hemodynamic and arterial stiffness parameters following reductions of dialysate calcium concentrations in patients undergoing hemodialysis. METHODS: In this prospective study, 20 patients on maintenance hemodialysis (10 females, 10 males) with dialysate calcium concentrations of 1.75 mmol/L were enrolled. At the start of the study, the dialysate calcium level was lowered to 1.50 mmol/L. Serial changes in biochemical, hemodynamic, and arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed every 2 months for 6 months. We also examined changes in the calcification-inhibitory protein, serum fetuin-A. RESULTS: During the 6-month study period, serum total calcium and ionized calcium decreased consistently (9.5 +/- 1.0 to 9.0 +/- 0.7, p = 0.002 vs. 1.3 +/- 0.1 to 1.1 +/- 0.1, p = 0.035). Although no apparent changes in blood pressure were observed, heart-femoral PWW (hf-PWV) and AIx showed significant improvement (p = 0.012, 0.043, respectively). Repeated-measures ANOVA indicated a significant effect of lowering dialysate calcium on hf-PWV (F = 4.58, p = 0.004) and AIx (F = 2.55, p = 0.049). Accompanying the change in serum calcium, serum fetuin-A levels significantly increased (95.8 +/- 45.8 pmol/mL at baseline to 124.9 +/- 82.2 pmol/mL at 6 months, p = 0.043). CONCLUSIONS: Lowering dialysate calcium concentration significantly improved arterial stiffness parameters, which may have been associated with upregulation of serum fetuin-A.
Aged ; Analysis of Variance ; Ankle Brachial Index ; Arteries/*drug effects/physiopathology ; Biological Markers/blood ; Blood Pressure/drug effects ; Calcium/*administration & dosage/adverse effects ; Compliance ; Female ; Hemodialysis Solutions/*administration & dosage/adverse effects/chemistry ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulsatile Flow/*drug effects ; *Renal Dialysis ; Republic of Korea ; Time Factors ; Treatment Outcome ; alpha-2-HS-Glycoprotein/metabolism