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Introduction: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end‑stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population., Objectives: We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD., Patients and Methods: We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI‑1), stromal cell‑derived factor 1α (SDF‑1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high‑sensitivity C‑reactive protein (hs‑CRP), ferric reducing ability of plasma, 2,2‑diphenyl‑1‑picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin‑A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF‑β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen., Results: We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca × Pi product, hs‑CRP, fibrinogen, SDF‑1α, PAI‑1, and sTM. However, PAI‑1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca× Pi product, and hs‑CRP levels., Conclusions: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF‑1α, PAI‑1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers.

Purpose: During the transition from premenopause to postmenopause, many women experience weight gain and central fat deposition; therefore, we hypothesized that circulating growth factors can play a role in the pathogenesis of hypertension, metabolic syndrome, and subclinical organ damage in perimenopausal women., Basic Procedures: The study included 192 women aged 40 to 60years; 152 had newly diagnosed essential hypertension that had never been treated, and 40 were normotensive age-matched controls. For all subjects, 24-h ambulatory blood pressure monitoring (ABPM), echocardiographic examination with assessment of left ventricular mass (LVM) and systolic and diastolic functions (GE Vivid 7.0, General Electric Vingmed Ultrasound, Horten, Norway), carotid ultrasound with measurement of intima-media thickness, and carotid-femoral pulse wave velocity (PWV) measurement (SphygmoCor, AtCor Medical, Sydney, Australia) were performed. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), and insulin-like growth factor-binding protein 3 (IGFBP-3) were measured using an immunochemical assay., Main Findings: Hypertensive women had significantly lower IGFBP-2 levels than did normotensive controls (162.9±83.7 vs. 273.1±103.0μg/L, p<0.001); the groups did not differ regarding IGF and IGFBP-3 concentrations. After adjusting the covariates, multivariate analysis showed that IGFBP2 was significantly negatively correlated with 24-h systolic blood pressure (β=-0.31, p=0.02). The adjusted odds ratio for hypertension per standard deviation decrease in IGFBP-2 was 3.43 (95% confidence interval [CI] 1.65-7.13). IGFBP-2 showed a negative correlation with the number of metabolic syndrome components. Independent of body composition, IGFBP-2 was significantly related to left ventricular relative wall thickness and the ratio of mitral inflow velocities as parameter of diastolic function., Principal Conclusions: In perimenopausal women, decreased IGFBP-2 levels may play a role in blood pressure regulation and the development of subclinical left ventricular diastolic dysfunction. Whether IGFBP-2 is a marker or a mediator of cardiovascular disease in this population merits further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients., Patients and Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CACS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations. Cardiovascular and overall mortality data were collected during a 7-years follow-up., Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age., Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality., (Copyright © 2016 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD)., Methods: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red., Results: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]., Conclusions: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Objectives: Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters., Materials and Methods: The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified., Results: Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age., Conclusions: The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

Unlabelled: In the last few years much attention is being given to the problem of diabetes mellitus, to it's development, prevalence and progression of chronic complications. The aim of the study was to 1. evaluate correction of metabolic disturbances in patients with long-term type 1 diabetes mellitus; 2. evaluate occurrence of diabetic nephropathy and excretion function in patients with long-term type 1 diabetes mellitus; 3. evaluate function of the cardiovascular autonomic nervous system in patients with long-term type 1 diabetes mellitus; 4. search for connections between the type and change dynamics in the cardiovascular system and degree of diabetic nephropathy advancement. The study was performed in a group consisting of 31 patients with type 1 diabetes mellitus (20 women, 11 males). Mean age of the study group equaled 37.6 +/- 10.75 years, duration of diabetes mellitus 21.3 +/- 9.55 years. Concentration of cystatin C in the study group was 0.98 +/- 0.23 ng/ml, in the group of patients with diabetic retinopathy 1.13 +/- 0.30 ng/ml, while in the group without diabetic retinopathy 0.89 +/- 0.13 ng/ml. Concentration of cystatin C (p <0.05) and calculated GFR according to equations proposed by F.J. Hoeck [GFR/1.73 m2 = -4.32 + 80.3/plasma cystatin] (p < 0.01) also G.D. Tan [GFR -10 = (87.1/plasma cystine) - 6.87] (p < 0.01) significantly differentiated the discussed groups., Conclusions: despite normal levels of blood creatinine in the studied patients, decreased glomerular filtration was calculated for plasma cystatin C. Plasma cystatin C concentrations and calculated glomerular clearance significantly differentiated the group with retinopathy from the group without diabetic retinopathy. Determining cystatin C concentrations as a protein which probably does not undergo glycation in plasma, may play a role in the detection of early diabetic nephropathy, when as well as plasma creatinine levels and albumin/creatinine index calculated from a sample of morning urine do not differentiate the studied group of patients.