Marcin Krzanowski

Relationship between aortic pulse wave velocity, selected proinflammatory cytokines, and vascular calcification parameters in peritoneal dialysis patients.

Introduction: Vascular calcification and arterial stiffening are cardiovascular risk factors among chronic kidney disease patients. Elevated aortic pulse wave velocity (AoPWV) is an independent predictor of increased cardiovascular morbidity and mortality. Objectives: The aim of the study was to analyze the relationships between inflammatory and vascular calcification parameters and arterial wall stiffness in chronic kidney disease (CKD) patients treated by peritoneal dialysis. Patients and methods: The study included 57 patients (27 women and 30 men) aged from 19 to 75 years (mean age 53 ± 13), treated by peritoneal dialysis during 4–100 months (mean 30.4 months). The concentrations of albumin, lipids, interleukin-6 (IL-6), IL-18, high-sensitive C-reactive protein, transforming growth factor-&bgr;1 (TGF-&bgr;1), osteocalcin, osteoprotegerin (OPG), fibroblast growth factor 23, fetuin A, parathyroid hormone (iPTH), total calcium (Ca), and phosphates (Pi) were measured. AoPWV was performed using a tonometric method, common carotid artery intima–media thickness (CCA-IMT) by ultrasonography evaluation, and calcium scoring (CaSc) with multirow spiral computed tomography (MSCT). Results: In univariate analysis, AoPWV correlated negatively with osteocalcin (R = −0.37; P = 0.005) and positively with OPG (R = 0.41; P = 0.002). Additionally, AoPWV was significantly positively associated with inflammatory parameters: IL-6 (R = 0.35; P = 0.009), TGF-&bgr;1 (R = 0.27; P = 0.047), and white blood cell (WBC) count (R = 0.33; P = 0.01). There were also positive correlations between AoPWV and imaging data: CCA-IMT (R = 0.32; P = 0.02) and CaSc (R = 0.38; P = 0.004). AoPWV did not correlate with calcium, phosphate, Ca × Pi index, or iPTH concentration. After multiple adjustments, osteocalcin was the only significant predictor of AoPWV. In logistic regression adjusted for age, hypertension, and mean arterial pressure at AoPWV evaluation, only osteocalcin was significantly associated with high (above median) AoPWV values [odds ratio 0.96 (0.92–0.99) per unit increase in osteocalcin]. Conclusion: OPG concentration and some inflammatory markers (WBC count, IL-6, TGF-&bgr;1) influenced the severity of arterial wall stiffness in CKD patients. Measurement of osteocalcin seems to be the best predictor of AoPWV.

Vascular Effects of Advanced Glycation End-Products: Content of Immunohistochemically Detected AGEs in Radial Artery Samples as a Predictor for Arterial Calcification and Cardiovascular Risk in Asymptomatic Patients with Chronic Kidney Disease

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 patients 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.

Impaired Fasting Glucose and Diabetes as Predictors for Radial Artery Calcification in End Stage Renal Disease Patients

Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20–24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death.

Risk Stratification in Dialysis Patients: Coronary Artery Calcification Score Combined with High Sensitive C-Reactive Protein and Framingham Score for Cardiovascular Risk Prediction in Asymptomatic Subjects

Introduction: Vascular calcification independently predicts cardiovascular disease, the major cause of death in Chronic Kidney Disease (CKD) patients. Coronary Artery Calcium Score (CACS) is a marker for atherosclerotic plaque burden, vascular calcification and has been shown to be a predictor of incidence of myocardial infarction and death from Cardiovascular (CV) disease. Objectives: The aim of the study was to evaluate factors influencing CV mortality in a group of Peritoneal Dialysis (PD) patients during a six year observation period. Patients and methods: The study included 53 patients with no symptoms of CV disease (25 women, 28 men; mean age of 52 ± 12 years) treated with PD for a median period of 24 months. Baseline Framingham Risk Score (FRS) was assessed and CACS was measured using Multi-Row Spiral Computed Tomography (MSCT). Laboratory measurements included high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), osteopontin (OPN), osteocalcin (OC), intact parathyroid hormone (iPTH), total calcium (Ca) and phosphates (Pi). The data concerning mortality was collected over a 6 year period. Results: During the six year observation period, 24 (45%) patients died, including 19 due to CV causes. Median overall survival was 72 months (lower quartile, 17 months). CACS was a significant predictor of all-cause and CV mortality both in simple analysis (HR=1.03 per 100 Agatston units, p=0.02 and HR=1.05, p=0.003), as well as in a multiple model adjusted for age of patients, dialysis duration, weekly creatinine clearance, Ca x Pi, iPTH, OPG, hsCRP and FRS (HR=1.04, p=0.02 and HR=1.05, p=0.01). The value of 800 Agatston units significantly differentiated the group into those with higher and lower risk for CV death (p=0.04). Age and FGF23 concentration were independent predictors of CACS. Also, hsCRP and FRS significantly predicted all-cause and CV mortality in simple Cox regression (HR=1.04, p=0.002 and HR=1.04, p=0.003; HR=1.14, p=0.047 and HR=1.23, p=0.01) as well as in a multiple model (HR=1.05, p=0.002 and HR=1.05, p=0.01; HR=1.23, p=0.01 and HR=1.33, p=0.004). Adding CACS to FRS and hsCRP significantly improved the prediction of cardiovascular mortality (p=0.02). Conclusions: Coronary calcium imaging is a non-invasive method of CV risk stratification that can accurately identify high-risk asymptomatic dialysis patients at the start of dialysis. The assessment of CACS together with inflammatory markers and conventional CV risk factors (FRS) may contribute to early diagnosis, prevention and reduction of deaths from CV disease in dialysis patients. Among the markers of bone disease, FGF-23 (a regulator of phosphorus metabolism) may be an early predictor of vascular calcification among dialysis patients.

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification: Elevated OPG Levels in HD Patients With Artery Calcification

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima‐media thickness (CCA‐IMT). Moreover, we studied the relationship between OPG levels and all‐cause and cardiovascular (CV) mortality during a 5‐year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C‐reactive protein, interleukin‐6, tumor necrosis factor receptor II (TNFRII), transforming growth factor‐β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA‐IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39–20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA‐IMT values (OR 6.56; 95%CI 1.06–40.6; P = 0.036). OPG levels above the median were associated with higher CCA‐IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84–72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA‐IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow‐up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA‐IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all‐cause mortality in CKD patients with advanced medial arterial calcification.

Isolated carotid artery fibromuscular dysplasia unifocal type diagnosed in the postpartum period

Fibromuscular dysplasia (FMD) is an idiopathic noninflammatory and nonarteriosclerotic segmental disorder of almost every arterial bed, leading to arterial sclerosis, occlusion, aneurysm, or dissection. It occurs most frequently in renal (80%), extracranial carotid and vertebral arteries (25–30%). Isolated intracranial FMD develops in 8.3% of patients. Carotid artery FMD is typically located bilaterally, in the middle and distal parts of the carotid artery [1, 2]. There are two characteristic angiographic types of FMD: multifocal with a typical string-of-beads appearance; and unifocal, characterized by stenosis [1]. Patients with carotid or vertebral artery FMD present with numerous nonspecific symptoms. However, specific neurological signs, such as transient ischemic attack, Horner syndrome, cranial nerve palsies, cerebral infarction, amaurosis fugax, and subarachnoid hemorrhage, may also be observed [3]. A 39-year-old woman with Graves disease, after radioisotope therapy, and suffering from polycystic ovary syndrome, was admitted to the hospital due to paraparesis reported on the third day postpartum. Two years earlier she suddenly developed transient right Horner syndrome, alteration in the bitter taste (a symptom of dysgeusia), and right mandible and ear pain. Duplex ultrasound (DUS) performed 10 days after the neurological episode revealed occlusion of the right internal carotid artery (RICA) with very limited blood flow, similarly to computed tomography angiography (CT angiography). No tear or blood accumulation was revealed. At the beginning of her third pregnancy, she experienced periodic episodes of paresthesia of her right upper and lower extremities. Approximately during the 18th week of pregnancy, the symptoms of paresthesia in her left leg and arm became more pronounced. Finally, due to the loss of sensation on the left side of her body and proprioception, a caesarean section was performed in the 30th week of pregnancy. An unexpected increase in blood pressure (200/110 mm Hg) following the administration of angiotensin-converting-enzyme inhibitors was observed. During hospitalization, all neurological symptoms gradually resolved. Another DUS examination showed a narrow RICA with an irregular lumen. No other changes constricting the lumen were detected. Computed tomography angiography revealed patent (1–2 mm) tortuous course of the right extracranial carotid artery (Figures 1 A, B), patent (1–1.8 mm) intracranial carotid artery with dilation to 2.5 mm in its cavernous part (Figure 1 C), and well-developed compensatory circulation from the circle of Willis via the anterior and posterior communicating arteries (Figure 1 D). The unifocal type of FMD was diagnosed. No changes in the vertebral or renal arteries and no other abnormalities in the circle of Willis were detected. The patient’s clinical condition significantly improved with resolution of neurological symptoms, and blood pressure was well controlled with amlodipine (110/80 mm Hg on average). Because of the compensatory circulation and the lack of neurological symptoms, no balloon angioplasty was performed. Interestingly, in this case, spontaneous carotid artery dissection (SCAD) may be superimposed on FMD, which has been observed in up to 90% of SCAD patients. Unfortunately, even angiography may be inadequate to differentiate the cause of the artery narrowing [4]. Perhaps the pregnancy was a trigger of the second episode of neurological symptoms.

Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients

Abstract Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.