Cardiovascular complications - 2

CYCLIC STRAIN OF HUMAN VASCULAR SMOOTH MUSCLE CELLS IN LONG-TERM CULTURES INCREASED EXPRESSION OF THE CALCIUM-SENSING RECEPTOR AND WAS ASSOCIATED WITH REDUCED CALCIFICATION TOP 20% ABSTRACTS

Abstract

INTRODUCTION AND AIMS:

Progressive arterial calcification is a major cause of cardiovascular mortality in patients with chronic kidney disease. We have recently demonstrated expression of the calcium-sensing receptor (CaSR) in human aortic smooth muscle cells (HAoSMC) and human arteries and demonstrated a correlation between CaSR expression and medial calcification. Here we investigated the role of SMC phenotype, pro-inflammatory factors and pulsatile strain in the development and progression of vascular calcification and CaSR expression.

METHODS:

HAoSMC were cultured for up to 4 weeks in the presence of 5mM b-glycerophosphate (b-GP) or 20ng/ml TNF-a alone or in combination. CaSR and a-actin (SMC marker) protein expression was analysed using Western blot. Cells were stained with alizarin red to assess calcification. In addition, cells were cultured under a cyclic biaxial strain (7% stretch, 30 cycles/min) using Flexcell apparatus and collagen I coated dishes for up to 14 days. Statistical analysis was performed using one-way ANOVA followed by Tukey's multiple comparison tests.

RESULTS:

Long-term culture of HAoSMC resulted in a gradual decline in smooth muscle a-actin expression, which decreased by 35% (p<0.05) after 2 weeks and >60% (p<0.01) after 4 weeks of culture. This was accompanied by a 45% reduction in CaSR protein expression (p<0.05). SMC a-actin expression decreased further following incubation for 4 weeks with b-GP (79%, p<0.05) or TNF-a (65%, p<0.05). This was not further altered by co-treatment with b-GP and TNF-a. No further change of CaSR protein expression was observed following incubation with b-GP or TNF-a. Alizarin red staining revealed larger areas of calcification in b-GP and TNF-a treated cultures after 4 weeks of treatment when compared to control cells; however, this increase was not significant. Culture of HAoSMC under cyclic strain produced a significant up-regulation of a-actin expression by day 7 and 10 (maximum 23%, p<0.05) compared to control static cultures. CaSR expression in strained cells was also increased by 45% by day 14 (p<0.05). Interestingly, alizarin red staining of 7 and 14 day cultures revealed significantly smaller areas of calcification in strained cells compared to control cultures (p<0.05).

CONCLUSIONS:

These data indicate that long-term static culture of HAoSMC results in a phenotypic change towards a calcification-promoting phenotype, which was accelerated in an inflammatory environment and was accompanied by reduced CaSR expression. In contrast, culture of cells under cyclic strain maintained the SMC phenotype, prevented calcification and was associated with increased CaSR expression. Of particular interest is the alteration in expression of the CaSR, which supports the hypothesis that the CaSR plays a key role in SMC calcification.This abstract is presented as Free Communication on 26-May-09 during the session Vascular calcification in renal disease.

THE MECHANISMS OF ENDOTHELIAL DYSFUNCTION IN HUMAN RESISTANCE ARTERIES OF CHRONIC KIDNEY DISEASE (CKD) TOP 20% ABSTRACTS

Abstract

INTRODUCTION AND AIMS:

Endothelial dysfunction (ED) has been suggested to play a role in the pathology of CKD and later adverse cardiovascular events. However, the mechanisms that confer the ED at the level of resistance vasculature in CKD have yet to be determined. The aim of this study was to establish the relative role of NO and endothelium-derived hyperpolarizing factor (EDHF) in the control of endothelial function in isolated resistance arteries from patients with CKD stage 5.

METHODS:

During the surgical procedure of catheter insertion subcutaneous fat was taken in 21 CKD stage 5 patients (15 males; median age: 58, range: 22-79 yrs). Subcutaneous fat biopsies were also obtained from 18 age- and sex-matched non-CKD patients (12 males; median age: 58, range: 29-77 yrs) undergoing elective hernia repair or laparoscopic cholecystectomy. Isolated arteries (~200μm) were mounted in a wire-myography system or prepared for transmission electron microscopy (TEM). Concentration response curves to bradykinin (BK), acethylcholine (ACh, 1nM - 3μM) and sodium nitroprusside (SNP, 0.1μM-0.1mM) were obtained. For the assessment of precise contribution of NO, EDHF and gap junctions to endothelium-dependent responses, pharmacological inhibitors for the specific pathways(N^w-nitro-L-arginine-methyl ester [L-NAME, 300μmol/L]; the cyclooxygenase inhibitor, indomethacin [Indo, 10µmol/L] and 18-α-glycyrrhetinic acid [18-αGA, 100μM], respectively) were applied.

RESULTS:

Endothelium-dependent relaxation to ACh was reduced in CKD patients (maximum % relaxation: 84±4 in CKD vs 94±1 in controls, P=0.02). Response to more physiological endothelium-dependent agonist BK was also reduced (maximum % relaxation: 76±4 in CKD vs 93±1 in controls, P=0.001). Vasodilatation to SNP was similar between arteries from CKD patients and controls. The part of endothelium-dependent relaxation resistant to L-NAME+Indo and referred as an EDHF-typed response was a prevalent component of the relaxation to ACh and BK in both groups (~85% from the total response). Pharmacological disruption of gap junctions with 18-aGA and confirmation of intercellular contacts between endothelial and smooth muscle cells with TEM suggests that myoendothelial gap junctions act as a main pathway for EDHF-typed responses in arteries from both CKD and control subjects. No differences in EDHF-typed responses were observed between arteries from both groups (i.e. % residual ACh-induced relaxation: 73±3 in CKD vs 73±3 in controls, P=0.6).

CONCLUSIONS:

Whereas overall endothelium-dependent relaxation is impaired in resistance subcutaneous arteries in CKD stage 5 patients, EDHF-typed responses are preserved. Thus, at level of resistance vasculature ED specific for CKD is characterized by reduced production and/or bioavailability of NO.This abstract is presented as Free Communication on 24-May-09 during the session Endothelial dysfunction and repair.

HIGH RESOLUTION CORONARY MR ANGIOGRAPHY FOR THE DETECTION OF PROXIMAL CORONARY STENOSIS IN CKD PATIENTS TOP 20% ABSTRACTS

Abstract

INTRODUCTION AND AIMS:

Chronic kidney disease (CKD) patients exhibit an increased cardiovascular mortality. However, the diagnostic algorithms for the detection of coronary artery disease (CAD) have been validated in non-CKD patients. They exhibit less sensitivity and specificity in CKD patients. Thus, new non-invasive methods are clearly warranted for cardiac risk stratification in these patients with a high risk of developing accelerated CAD. High resolution magnetic resonance angiography (MRA) without contrast agent serves as a novel diagnostic tool to analyse the proximal part of the coronaries. So far, there are no data concerning this method in CKD patients.

METHODS:

In this pilot study we examined the reliability of MRA (3D SSFP) without contrast agent for the detection of CAD in 15 CKD patients (GFR < 30 ml/min) with an indication for conventional coronary angiography. Fourteen MRAs of the proximal coronaries were analysed for stenoses >50% by investigators who were blinded to the results of the coronary angiography. MRA results were then compared to the results of the conventional coronary angiography to obtain sensitivity, specificity, positive and negative predictive values.

RESULTS:

We detected 13 stenoses in 10 patients (table 1, sensitivity 81%, specificity 95%). Stenoses of the left main coronary artery could be detected reliably (sensitivity 100%, specificity 100%) whereas the detection of stenoses of the left circumflex artery was more difficult (table 1). Based on the MRA results only as a screening test, all patients with significant CAD would have undergone subsequent invasive angiography (sensitivity 100%, specificity 75%, positive and negative predictive values 87% and 92%, respectively, for the presence of a relevant CAD).

CONCLUSIONS:

High resolution MRA without contrast agent may serve as a reliable diagnostic tool for the detection of proximal stenoses in CKD patients and can help in the decision process for an invasive coronary angiography. This novel technique has the potential to become part of the routine non-invasive diagnostic algorithm for CAD detection in CKD patients.

DECREASE IN SKIN MICROCIRCULATION DURING HEMODIALYSIS (HD) PREDICTS DEVELOPMENT OF SKIN DEFECTS TOP 20% ABSTRACTS

Abstract

INTRODUCTION AND AIMS:

Ischemic non-healing wounds are frequent problem in patients on chronic hemodialysis (HD). Malnutrition, inflammation and atherosclerosis (MIA) syndrome can lead to peripheral ischemic skin defects. The aim of present study was to estimate the influence of peripheral blood flow changes on development of foot defects in HD patients.

METHODS:

Peripheral skin blood flow was measured using Laser Doppler Line Scanner (LDLS®, Moor, Devon, UK) in 10 different areas (AI) of dorsal part of instep and fingers of each foot before and during HD ultrafiltration (897±465 mL) in 31 HD patients (10 female, 21 male; age 36-79 y, BMI= 28±5.0). No peripheral skin defects or apparent acute disease or infection were detected in any patient at the time of LDLS measurement. Foots of patients were carefully clinically re-examined 18 months later.The cutt-off value for critically low skin perfusion was determined as a skin blood flow after inflating the cuff of sfygmomanomether above systolic blood pressure in 15 patients (biological zero).For statistical analysis two-sample t-test, one-way ANOVA, Pearson correlation coefficient and Kaplan Meier log-rank analysis were applied (Sigmastat 3.1; SPSS, Inc, San Jose, CA, USA).

RESULTS:

We have found significant and constant decrease of skin blood flow during HD (p<0.001). Skin microcirculation before HD as well as during HD correlated with serum albumin (before HD: r=0.36, p=0.05; during HD: r=0.47, p=0.007). Nine patients developed a skin defects during the follow-up period. Peripheral blood flow in these subjects was significantly lower compared to patients with no defects (see table; skin blood flow expressed in arbitrary unit).

Significantly larger proportion of patients with normal perfusion remained defect-free in comparison to patients with critical perfusion (93% vs. 38%, p=0.002, Kaplan Meier analysis).

CONCLUSIONS:

Skin blood flow may be impaired in HD patients and HD procedure leads to further decrease, often below critical value. Low skin blood flow in dialysis patients may predict future development of skin defects. Hemodialysis strategy should include not only adequate solute removal, but also appropriate fluid handling, not allowing the critical peripheral perfusion.

BRAIN NATRIURETIC PEPTIDE IN HEMODIALYSIS PATIENTS: PREDICTIVE VALUE FOR ALL-CAUSE AND CARDIOVASCULAR MORTALITY TOP 20% ABSTRACTS

Abstract

INTRODUCTION AND AIMS:

Brain natriuretic peptide (BNP) is a predictor of mortality in multiple cardiovascular (CV) diseases but its value in haemodialysis (HD) patients is still a matter of debate. The aim of this observational and prospective study was to evaluate the role of BNP as a prognostic factor in terms of all-cause and CV mortality in HD patients treated in a single centre.

METHODS:

We measured BNP concentration before HD in 125 prevalent HD patients (mean age at beginning of HD 48.80±14.95 years, mean haemodialysis vintage 99.26±60.77 months) to examine the two years all-cause and CV mortality associated with baseline BNP concentrations. Sensitivity, specificity and cut-off levels for pre-HD BNP as predictor of all-cause and CV mortality were analyzed by means of receiver operating characteristic (ROC) curve.

RESULTS:

The mean pre-HD BNP value was 1621.25±2995.16 pg/ml (103.1 - 29190). During the 2-year follow-up, 35 out of 125 patients (28 %) had died, most from CV diseases (65.7%). Patients who died of CV causes had higher levels of BNP (3736.61±6239.16 vs. 1112.08±1132.13; p=0.0002), as well as patients who died of all causes (2947.86±5178.76 vs. 1105.35±1136.64; p=0.0017). There was a positive correlation between BNP and systolic blood pressure (SBP) (r=0.302, p=0.0006), pulse pressure (PP) (r=0.354, p=0.0000), left ventricular mass index (LVMI) (r=0.356, p=0.0002), left ventricular volume index (r=0.243, p=0.012), and inverse correlation between BNP and haemoglobin (r=-0.329, p=0.0001), creatinine (r=-0.284, p=0.0013) and ejection fraction (r=-0.201, p=0.041). Patients with BNP>1200pg/ml had significantly higher SBP (145.38±33.67 vs 128.73±20.42mmHg, p=0.000), PP (60.53±16.03 vs 49.39±11.32mmHg, p=0.000), C-reactive protein (12.13±11.28 vs 7.86±6.44mg/l, p=0.007), LVMI (160.91±22.76 vs 127.27±39.28, p=0.000g/m2) and significantly lower haemoglobin (103.71±9.92 vs 110.91±9.40g/l, p=0.000) than those with BNP<1200pg/ml. The cut-off point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1115.45 pg/ml for all-cause and 1193.5pg/ml for CV mortality. Kaplan-Meier analysis showed that all cause (log rank, p=0.0002) and CV mortality (log rank, p=0.0012) were the cause for a significantly lower survival in patients with mean BNP levels >1200 pg/mL.

CONCLUSIONS:

Our results suggest that basal BNP plasma levels are a useful non-invasive marker of long term mortality in HD patients. Identifying HD patients with BNP>1200 pg/ml, at increased risk of cardiac events, may improve their prognosis.

INFLAMMATION CAUSES STATIN RESISTANCE IN VITRO AND IN VIVO: A POTENTIAL MECHANISM FOR INEFFECTIVENESS OF STATIN THERAPY

Abstract

INTRODUCTION AND AIMS:

HMGCoA reductase is an important rate-limiting enzyme for cholesterol biosynthesis and the target for cholesterol lowering drug statins which lower plasma cholesterol concentrations by upregulating hepatocyte LDL receptors. The clinical effects of statins may be reducing in patients with chronic inflammatory diseases, such as those with renal dysfunction and type 2 diabetes. Since inflammatory stress plays an important role in dysregulating intracellular cholesterol homeostasis, the present study was carried out to investigate whether a degree of resistance to statins is present in the presence of inflammatory stress.

METHODS:

We used IL-1β stimulation in human hepatoblastoma cell line (HepG2) cells and human kidney mesangial cells (HMCs) to induce inflammatory stress in vitro and the concentration of statins required for 50% inhibition of HMGCoA reductase activity (IC50) was calculated. Eight-week old ApoE/Scavenger receptor typeA/CD36 triple knockout (KO) mice fed a Western Diet were randomly assigned to either daily subcutaneous injections of 10% casein to induce inflammation or vehicle. Animals were sacrificed after 14 weeks and terminal blood samples were assayed for lipid profile, serum amyloid A (SAA) and TNFα. Liver, aorta and kidney were harvested and tissue lipid levels measured by enzymatic assay and Oil Red O staining.

RESULTS:

LDL loading reduced HMGCoA reductase mRNA, its protein expression, enzymatic activity and intracellular cholesterol synthesis in vitro. However, these suppressive effects were overridden by IL-1β, suggesting that IL-1β disrupts HMGCoA reductase physiological feedback regulation. Mevatatin inhibited HMGCoA reductase activity by 50% (IC50) at concentrations of 30 mM for HepG2 cells and 8 mM for HMCs, but at the same concentration of mevastain in the presence of IL-1β, we observed only 28% and 30% inhibition of HMGCoA activity in HepG2 cells and HMCs respectively. In vivo, casein injected mice required atorvastatin 10mg/kg/day to obtain the same effect as a 2mg/kg/day dose in non-casein injected mice, to attain similar levels of serum total cholesterol (TC)and LDL cholesterol. Serum SAA and IL-6 were also higher in the casein injected mice given atorvastatin 2 mg/kg/day compared with mice receiving atorvastatin of 10 mg/kg/day. Lipid accumulation in the liver, aorta and kidney was more extensive in casein-injected animals. Atorvastatin 2 mg/kg/day reduced lipid accumulation in kidney in non-casein injected mice, but higher doses of atorvastatin (10 mg/kg) were required to achieve an equivalent effect under inflammatory stress, suggesting that inflammatory stress causes atorvastatin resistance.

CONCLUSIONS:

Inflammation overrides the suppression of HMGCoA reductase activity by statins and causes statin resistance in vitro and in vivo. Hence a higher concentration of statin may be required to achieve the same biological and clinical effects in inflammatory states.

ASSOCIATION OF KIDNEY FUNCTION WITH CIRCULATING ANGIOPOIETIN-2 LEVEL

Abstract

INTRODUCTION AND AIMS:

Angiopoietin (Ang)-1 and Ang-2 are mutually antagonistic ligands of the endothelial-specific Tie2 receptor. As a gatekeeper of endothelial activation, the Ang-Tie system plays an important role in atherosclerosis. In chronic kidney disease (CKD) patients on dialysis, circulating Ang-2 levels were markedly increased and correlated with atherosclerotic burden. However, if the elevation of Ang-2 levels is a direct consequence of impaired renal function or if this phenomenon simply reflects the present vascular burden is unknown. Aim: To study the relevance of renal function on circulating Ang-2 evaluating CKD patients, renal transplant recipients (RTR) and healthy living kidney donors.

METHODS:

First, serum Ang-2 (ELISA) and traditional cardiovascular risk factors were assessed in 44 untreated nonsmokers at different stages of CKD (1-4). Glomerular filtration rate (GFR) was assessed by the inulin-clearance technique. Ang-2 was also measured in 14 stage 5 CKD patients on haemodialysis. For comparison, 29 healthy subjects were examined. Second, 14 RTR were longitudinally assessed immediately before transplantation and 3 months thereafter. Third, we quantified Ang-2 in 7 healthy individuals during 7 days after living kidney donation (0, 3, 6, 12, 24, 72, and 168 h).

RESULTS:

(1) Compared to controls (0.9 ± 0.68 ng/mL) serum Ang-2 levels started to increase significantly at stage 3 CKD (stage 1: 1.0 ± 0.61; stage 2: 0.97 ± 0.27; stage 3: 1.32 ± 0.77*; stage 4: 1.9 ± 0.82*; stage 5: 7.23 ± 4.4* ng/mL). Further, Ang-2 levels correlated inversely with the GFR (r=-0.449, p=0.002).(2) Circulating Ang-2 levels in RTRs significantly declined after transplantation (before 5.47 ± 8.1 vs. 2.15 1.1 ng/mL, p=0.01).(3) The healthy kidney donors showed no increase in Ang-2 during the first 2 post-op days, indicating no direct Ang-2 relation to surgical trauma. However, consistent with the loss of 50% renal mass, we noted a significant increase in serum Ang-2 already 3 days after donation (1.43 to 2.45 ng/mL, p=0.001).

CONCLUSIONS:

Elevated Ang-2 concentrations are present in patients with higher CKD stages and correlate inversely with the GFR. Even in RTRs and living kidney donors the tight connection between renal function and Ang-2 could be demonstrated. Thus, Ang-2-driven endothelial activation might be a new molecular mechanism for accelerated atherosclerosis and excessive cardiovascular risk in CKD patients.

SERUM NON-TRANSFERRIN BOUND CATALYTIC IRON AND ITS RELATION TO CARDIOVASCULAR DISEASE IN PATIENTS ON MAINTENANCE HEMODIALYSIS

Abstract

INTRODUCTION AND AIMS:

Cardiovascular disease has a great impact on morbidity and mortality on patients with chronic kidney disease (CKD) specially those undergoing renal replacement therapy (RRT). CKD is a state of oxidative stress. Non-transferrin bound serum catalytic iron (SCI) catalyses the formation of reactive oxygen species.Our aim was to assess SCI as a vascular marker for cardiovascular disease in patients on maintenance hemodialysis (MHD).

METHODS:

A prospective cross-sectional study was performed between October 2008 and January 2009. 53 ESRD patients on MHD (36 males&17 females) for at least 6 months duration, having mean age 55.52 ± 9.47 years were enrolled. Apart from detailed clinical history and examination of cardiovascular events and system the patients were evaluated by dobutamine stress echocardiogram (DSE), carotid intimal medial thickness (IMT) and coronary angiography (CAG). SCI was measured by Bleomycin assay described by Evans and Halliwell (1994), values of which are expressed as μmoles/L. Significant coronary artery disease (CAD) was diagnosed based on presence of ≥ 50% luminal narrowing in epicardial coronary arteries. The SCI was compared in MHD patients, normal population undergoing health survey (n = 290) and in patients with various stages of CKD, who were not on RRT (n = 70).

RESULTS:

Left ventricular hypertrophy was seen in 46 (86.8%) patients on MHD. Diastolic dysfunction was seen in 15 (28.3%) patients and 3 (5.66%) patients had systolic dysfunction. DSE was positive for inducible ischaemia in 9 (16.99%) patients. IMT was more than > 0.8 mm in 38 (71.7%) patients.Significant CAD was detected in 20 (37.7%) patients. Out of these 20 patients 9 patients had single vessel disease.SCI in patients on MHD was 4.7 ± 1.79 as compared to normal population 0.11± 0.01 (p<0.0001). In patients of CKD not on RRT, SCI was 1.21± 0.200, which is significantly lower than MHD patients (p<0.0001).

CONCLUSIONS:

Significant CAD was found in 37.7% patients on MHD. Significant left ventricular abnormality was found in 86.6% patients. SCI is significantly high in patients having positive DSE, significant CAD and patients having IMT > 0.8 mm. SCI increases with the severity of CAD. SCI appears to be a good vascular biomarker for CAD in patients on MHD.

BLOOD PRESSURE LOWERING REDUCES CARDIOVASCULAR EVENTS AND MORTALITY IN DIALYSIS PATIENTS: A SYSTEMATIC REVIEW OF RANDOMISED CONTROLLED TRIALS

Abstract

INTRODUCTION AND AIMS:

Patients receiving dialysis have markedly increased cardiovascular risk. Although blood pressure (BP) lowering trials have clearly demonstrated cardiovascular benefit in the general population, the efficacy and safety of BP lowering in dialysis patients are uncertain. We systematically reviewed all available randomised trials of BP lowering in dialysis patients.

METHODS:

MEDLINE, EMBASE and the Cochrane Library database were searched for trials reported between 1950 and November 2008, without language restriction. We extracted a standardised dataset from randomised controlled trials that employed any form of BP lowering in dialysis patients and reported cardiovascular outcomes.

RESULTS:

Eight trials involving 1679 patients and 495 cardiovascular events were included. In actively treated patients, weighted average systolic and diastolic BP levels were -4.5 mmHg and -2.3 mmHg lower, respectively. BP lowering was associated with a 29% (95% confidence interval (CI) 8 – 45%, p=0.009) lower risk of cardiovascular events, a 20% (CI 4 – 34%, p=0.014) lower risk for all-cause mortality and a 29% (CI 1 – 50%, p=0.044) lower risk for cardiovascular mortality as compared with control regimens. Heterogeneity (I²= 67.5% p=0.003) in the magnitude of the effect was observed for the outcome of all cardiovascular events, but not for all-cause mortality. The magnitude of risk reduction was similar for the different classes of BP lowering agents. Furthermore, the effects appear to be consistent irrespective of the presence or absence of hypertension or other co-morbidities.

CONCLUSIONS:

BP lowering agents significantly reduce the risk of cardiovascular events, all cause mortality and cardiovascular mortality in patients undergoing dialysis. These data suggest that administration of BP lowering agents should be considered routinely for individuals undergoing dialysis to reduce the very high cardiovascular morbidity and mortality rate in this population.

FETUIN-A, CARDIAC VALVE CALCIFICATION AND LEFT VENTRICULAR FUNCTION EVALUATED BY TISSUE DOPPLER IMAGING IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Hemodialysis (HD) patients have an increased incidence of calcification of all cardiac structures which may contribute to the development of left ventricular (LV) dysfunction and the high cardiovascular mortality observed in these patients. Fetuin-A is a serum protein that inhibits ectopic vascular calcification. Tissue Doppler Imaging (TDI) is a new echocardiographic technique that allows early detection of LV dysfunction. This study aimed at evaluating serum fetuin-A in stable HD patients and its relation to biochemical parameters, valvular calcification and alterations in LV function assessed by conventional echocardiography and TDI.

METHODS:

Fifty-two non-diabetic HD patients free from overt cardiac dysfunction (aged 50.4 ±10.6 years; mean HD duration, 47.4 ±16.2 months) and 32 healthy age- and sex-matched controls underwent clinical examination, routine biochemical tests and measurements of C-reactive protein (CRP) and serum fetuin-A. LV function was assessed by M-mode, two-dimensional, Doppler echocardiography and TDI.

RESULTS:

Serum Fetuin-A levels were significantly lower in HD patients than in controls. Cardiac valve calcifications were detected in 40% of HD patients (57 % aortic, 33 % mitral, 10 % combined). Compared with patients with normal fetuin-A (≥0.4 g/l, n=28), those with low fetuin-A (< 0.4 g/l, n=24) showed significantly longer time on dialysis, higher phosphate, higher CRP, lower albumin, higher prevalence of valvular calcification and diastolic dysfunction. Using conventional echocardiography, systolic and diastolic indices of LV function demonstrated similar values in HD patients and controls. However, using TDI, HD patients showed significant deterioration of indices of LV diastolic function of both interventricular septum and lateral wall than controls. TDI was able to identify significantly more HD patients with diastolic dysfunction than conventional echocardiography (19 vs 6 patients, P<0.05). LV septal and lateral wall early diastolic myocardial velocity (Em); the most sensitive TDI indicator of diastolic dysfunction, were significantly related to serum fetuin-A and negatively correlated with CRP and valvular calcification.

CONCLUSIONS:

Serum fetuin-A is significantly low in HD patients and cardiac valve calcifications are frequent in these patients. Low serum fetuin-A in HD patients shows significant associations with valvular calcification, inflammatory markers, low serum albumin and diastolic dysfunction. TDI shows early impairment of diastolic function in stable HD patients and seems to be a more sensitive technique than conventional echocardiography for early detection of LV diastolic dysfunction in these patients. In HD patients with low fetuin-A, more attention needs to be given to the control of factors associated with vascular calcification to reduce the risk of cardiovascular morbidity and mortality in dialysis patients.

INTRAVENOUS IRON SUPPLEMENTATION ASSOCIATES WITH CARDIOVASCULAR AND INFECTIOUS COMPLICTIONS IN CHRONIC HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Intravenous (IV) iron supplementation plays a pivotal role in the correction of anemia in hemodialysis (HD) patients. However, IV administered iron may provoke the generation of bioactive iron, aggravate endothelial dysfunction and impair phagocytic activity of neutrophils in HD patients. Therefore, we aim to assess the influence of cumulative IV iron dosage on cardiovascular (CV) and infectious outcome among chronic HD patients.

METHODS:

A cohort of 1311 chronic HD patients were recruited from 27 dialysis clinics, and baseline demographic, comorbidity, and laboratory measurements were recorded at enrollment. All patients were divided into two groups with (n= 523) or without (n= 788) IV administration of ferric chloride hexahydrate (Atofen®; Uji pharmaceutical Co. Ltd, Japan) 6 months following the enrollment. Iron-treated patients were further stratified into 3 subgroups according to the cumulative iron dose within 6 months: 40 to 400 mg (Group I, n= 462), >400 to 800 mg (Group II, n= 124) and >800 mg (Group III, n= 202), respectively. The group without IV iron treatment was defined as reference. In a mean follow-up of 18 months, CV and infectious deaths were recorded. Cox-proportional hazards models were used to characterize the adjusted relationship between cumulative iron dosage and outcome.

RESULTS:

Reference group had characteristics of young age, high ferritin and transferrin saturation, low serum albumin, and low percentage of DM and hypertension as compared with IV iron group (p<0.05). Compared with reference, group III showed a statistically significant higher CV death (adjust HR = 2.83; 95% CI 1.43–5.61, p<0.005) and CV events (adjust HR = 2.87; 95% CI 1.75–4.71, p<0.001), respectively. Similarly, statistically significant higher infectious death (adjust HR = 4.58; 95% CI 1.55–13.50, p<0.01) and events (adjust HR = 3.57; 95% CI 2.11–6.06, p<0.001) were observed in the group III while compared with reference. In contrast, cumulative iron dosage with 40–800 mg over 6 months showed a modest association with CV and infectious deaths, but associated with lower CV events than reference.

CONCLUSIONS:

Cumulative doses of IV ferric chloride hexahydrate with >800 mg over 6 months associate with increased CV and infectious risk for chronic HD patients. Therefore, caution is warranted when administrating high iron dose to HD patients in a short period due to greater CV and infectious morbidity and death.

UREMIC TOXINS AND VASCULAR INJURY HAVE A DISTINCT INFLUENCE ON ENDOTHELIAL PROGENITOR CELLS IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Patients suffering from chronic kidney disease exhibit cardiovascular diseases and profound endothelial dysfunction, which is reflected by reduced number of endothelial progenitor cells involved in vascular repair. Several issues remain unresolved regarding the factors influencing endothelial progenitor cell number during chronic kidney disease. Among these factors, we examined the influence of uremic toxins and vascular injury on endothelial progenitor cells in hemodialysis patients.

METHODS:

Thirty-eight hemodialysis patients were investigated and compared to 21 healthy controls. Among progenitor cells, CD34+CD133+ immature progenitors and CD34+KDR+ endothelial progenitors were quantified in peripheral blood by flow cytometry, and myeloid endothelial progenitor cells (mEPC), were counted after ex vivo culture. Levels of uremic toxins b₂-microglobulin, indole-3 acetic acid, indoxylsulfate, p-cresylsulfate, and homocysteine were measured. Vascular injury was assessed by plasma levels of endothelial microparticles and aortic pulse wave velocity.

RESULTS:

CD34+KDR+ endothelial progenitor and mEPC numbers were reduced in hemodialysis patients compared to healthy controls, respectively by 73% (p<0.0001) and 62% (p<0.001). We found a negative correlation between the uremic toxins b₂-microglobulin and indole-3 acetic acid, and CD34+CD133+ immature progenitor cells. Moreover, mEPC number was positively correlated with the markers of vascular damage, pulse wave velocity (p<0.001) and endothelial microparticle levels (p = 0.001).

CONCLUSIONS:

These results suggest that uremic toxins could have a deleterious role in the differentiation process of endothelial progenitors. Nevertheless, even in a context of decreased endothelial progenitor cell number, vascular lesions could still stimulate progenitor cell mobilization in hemodialysis patients.

NO IMPROVEMENT IN CARDIAC STRUCTURE AND FUNCTION IN ALTERNATE NIGHTLY HEMODIALYSIS

Abstract

INTRODUCTION AND AIMS:

Increased left ventricular volumes and mass are associated with adverse cardiovascular events in end stage renal disease patients. Preliminary data suggests nightly nocturnal haemodialysis may improve left ventricular mass and ejection fraction. We explored the hypothesis that alternate nightly home haemodialysis (NHD) improves cardiovascular structure and function whilst reducing burden on patients and costs.

METHODS:

Between 2003 and 2006, 63 patients (age 52±13 years, 79% male, duration of dialysis therapy (DTT) 1.8 (IQR 0.7-4.1) years, diabetes 33%) on conventional haemodialysis (CHD) (3-5 hours for 3.5-5 sessions weekly), converted to NHD (6-9 hours overnight for 3.5-5 sessions weekly). Cardiac morphology and function were assessed using 2 Dimensional transthoracic echocardiography performed post dialysis at baseline and 12-24 months after commencing NHD and comparison made with a control population of 63 patients who continued to receive CHD.

RESULTS:

In the NHD group, LV structure and function remained stable.

Measures of diastolic function remained stable including: early transmitral flow velocity (E): 0.80±0.25vs 0.79±0.28m/s, p=0.88; E/A ratio: 1.04±0.49 vs 1.06±0.37, p=0.77; deceleration time 227±57 vs 213±48 ms, p=0.06; annular tissue Doppler velocity (E'): 5.88±1.72 vs 5.73±1.85m/s, p=0.66. Markers of filling pressure remained stable - both acute (E/E' 14±4 vs 15±7, p=0.28) and chronic (LA volume 71 [IQR 58-93] vs 72 [IQR 61-91] mL, p=0.84). LV structure and function remained stable in the control group and there were no significant differences in the change in LV structure and function parameters between the NHD and control groups (table 1).These findings were maintained after adjustment using multivariate analysis for differences between the 2 groups in age, gender, duration on dialysis and diabetes. We note interdialytic weight gains increased with conversion to NHD: 2.3±0.8 vs 2.7±1.0kg, p=0.006.

CONCLUSIONS:

Unlike the previous results with daily dialysis regimens, alternate nightly NHD does not appear to result in improvement in LV dimensions and mass. The large interdialytic weight gains we observed with conversion to alternate nightly NHD may be one explanation for this difference. Future randomized controlled trials will be critical in determining if extended hours and increased frequency dialysis regimens really result in improved cardiac structure and function and in defining important differences between novel regimens.

LANTHANUM CARBONATE AND SEVELAMER HYDROCHLORIDE PREVENT VASCULAR CALCIFICATION IN UREMIC RATS

Abstract

INTRODUCTION AND AIMS:

In a clinical setting, phosphate binders represent a first line of treatment in uremic patients. In addition to its beneficial effect in controlling secondary hyperparathyroidism (SHPT), reduction in extracellular phosphate levels decreases the risk of vascular calcification (VC). This study compares the efficacy of two phosphate binders, lanthanum carbonate (LC, Fosrenol®) and sevelamer hydrochloride (SH, Renagel®), to prevent VC and reduce mortality in uremic rats.

METHODS:

5/6th nephrectomized Wistar rats fed a low (0.6%) phosphate (P) diet (LP) or high (1.2%) P diet (HP), were treated for 5 wks with calcitriol (CTR), 80 ng/kg i.p. q.o.d. (LP+CTR and HP+CTR). Two HP+CTR subgroups received 2% LC (equivalent to 1.05% w/w elemental lanthanum) or 2% SH in the diet. Serum bicarbonate, ionized calcium (Ca), P, PTH, Creatinine (Cr) as well as the aortic vascular content of Ca (CaAO) and P (PAO) were measured. 24-hr urine was used to measure P excretion.

RESULTS:

The study demonstrated a significant decrease in mortality with LC and SH (14/15 survived) compared with no phosphate binder (8/15 survived, HP+CTR group). Both LC and SH reduced urinary P excretion, but only LC reduced serum P. VC was similar in LC- and SH-treated rats but significantly lower than in rats treated with CTR alone. However, the dose of lanthanum used was lower compared to SH. SH administration resulted in a significant reduction in serum bicarbonate, which may in part account for its anti-calcifying effect. Serum PTH levels were controlled in both LC- and SH-treated rats (13.2±5.6 vs 12.5±2.5 pg/ml) respectively. Serum Cr was similarly increased in the group with the 5/6 nephrectomy.

CONCLUSIONS:

These findings indicate that both phosphate binders are equally effective in controlling hyperparathyroidism, and decreasing mortality and VC in an animal model of uremia with SHPT treated with CTR.

DISCLOSURE:

This study was sponsored by Shire Pharmaceuticals

PENTRAXIN 3 (PTX3) LEVELS ARE ASSOCIATED WITH CORONARY ARTERY DISEASE, PERIPHERAL ARTERY DISEASE AND ALL-CAUSE MORTALITY IN HEMODIALYSIS (HD)-PATIENTS

Abstract

INTRODUCTION AND AIMS:

Pentraxins are evolutionarily highly conserved proteins with a key role in innate immunity and inflammatory processes. While an association of the short pentraxin C-reactive protein (CRP) with cardiovascular disease is well described, there are less data for the role of the long pentraxin PTX3. We investigated the association between PTX3 and cardiovascular disease as well as mortality in HD-patients.

METHODS:

Plasma was obtained from 153 HD-patients after the long dialysis free interval. PTX3 and IL-6 levels were measured by ELISA kit (R&D, Wiesbaden, Germany). High-sensitivity CRP was determined by nephelometry. Clinical and demographic variables were recorded (presence of cardiovascular or coronary artery disease, stroke, infarction, age, dialysis vintage and residual renal function). Patients were followed for at least 25 months to analyze mortality.

RESULTS:

In HD-patients, PTX3 levels were significantly higher in patients with compared to those without coronary artery disease (3,13 ng/ml compared to 1,96 ng/ml, p=0,038) and peripheral artery disease (2,93 ng/m compared to 2,18 ng/ml, p=0,039). PTX correlated significantly positive with CRP (p=0,005) and IL-6 (p=0,007). There was a significant positive correlation between PTX3 and age (p=0,002), age at starting dialysis (p=0,025) and dialysis vintage (p=0,047). PTX3 correlated significantly negative with residual renal function (p=0,008). 30 patients (20%) died during the 25 month follow-up. 50 % of death were found in the 4th quartile of PTX3. We found a significant association between PTX3 (p=0.0001) as well as IL-6 (p=0.01) plasma levels and all-cause mortality in HD-patients CRP was not significantly associated with mortality.

CONCLUSIONS:

In HD patients, levels of PTX3 are associated with cardiovascular and peripheral artery disease. PTX3 levels predict future all-cause mortality and appears to be an even better predictor than CRP or IL-6.

FUNCTIONAL ABNORMALITIES OF ISOLATED RESISTANCE ARTERIES IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD)

Abstract

INTRODUCTION AND AIMS:

Vascular abnormalities are considered to play a key role in the rapid acceleration of adverse cardiovascular events in CKD. However, nothing is known about the functionality of the resistance vasculature, which is directly involved in the control of peripheral resistance, blood flow to target organs, and, as such, plays a major role for blood pressure control. The aim of the study was to utilize the isolated small artery bioassay to compare endothelial and smooth muscle function in resistance arteries obtained from CKD stage 5 patients and healthy controls.

METHODS:

Arteries (internal diameter 200mm) were dissected from subcutaneous fat biopsies obtained during the surgical procedure of catheter insertion in 18 CKD stage 5 patients starting peritoneal dialysis (14 males; median age 59, range 22-79 yrs) and 19 controls (12 males; median age 53, range 29-72 yrs) undergoing elective hernia repair or laparoscopic cholecystectomy. Isolated arteries were mounted on a pressure myograph in order to evaluate the effects of mechanical forces (increase in intraluminal pressure and flow-induced shear stress), responses to endothelium-dependent (acetylcholine [ACh]) and independent (sodium nitroprusside [SNP]) agonists, as well as passive distensibility.

RESULTS:

Flow-mediated dilatation was attenuated in arteries from CKD patients (e.g. % relaxation at flow rate of 140 μl/min: 37±4 in CKD [n=13] vs. 57±4 in controls, [n=16] p=0.0002). This was also accompanied by impaired dilatation to ACh (e.g. % relaxation to ACh at 1μM/L: 56±10 in CKD [n=13] vs. 84±5 in controls [n=11]; p=0.02), but preserved responses to SNP (% relaxation to SNP at 0.1mM/L: 67±24 in CKD [n=12] vs. 65±19 in controls [n=10] p=0.56). Myogenic tone developed in response to changes in intraluminal pressure was similar between the groups (e.g. at 120 mmHg 13±2% in CKD [n=17] vs. 12±2% in controls [n=18] p=0.88). However vascular distensibility was reduced in CKD (e.g. % distensibility at 120 mmHg: 190±15 in CKD [n=10] vs. 229±12 in controls [n=19], respectively; p=0.02).

CONCLUSIONS:

A number of functional abnormalities in the peripheral resistance vasculature are present in CKD stage 5 patients. The observed alterations may significantly amplify the common cardiovascular complications of CKD.

ADIPONECTIN AND ATHEROSCLEROSIS IN CHRONIC HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Atherosclerosis is a serious complication in patients undergoing chronic hemodialysis.The serum levels of adiponectin to the risk of development of arterial sclerosis and its treatment have not yet been fully clarified in hemodialysis patients.The present study was undertaken to examine the relationship between atherosclerosis and the serum levels of adiponectin in hemodialysis patients.

METHODS:

The subjects were 25 males and 24 females who had been undergoing chronic hemodialysis at our facility (age, 54.3 ± 13.8 years; duration of dialysis, 12.4 ± 9.6 years).Assessment of the background factors, blood pressure and visceral fat area, assessment of atherosclerosis, and collection of blood samples were conducted for each subject.The blood samples were collected before the first dialysis session of a week, 6 hours or more after the last meal, for measurement of adiponectin.The brachial ankle pulse wave velocity (baPWV) was measured as a marker of atherosclerosis using a blood pressure and pulse wave measuring device (Form PWV/ABI, Omron Colin, Kyoto, Japan).And the all patients were measured the baPWV after one year again.Serum adiponectin was measured by ELISA (Human Adiponectin ELISA Kit, Otsuka Pharmaceutical, Tokyo, Japan).Each parameter was expressed as the mean ± SD. Statistical analysis was performed using JMP Version 5.1 (SAS for Windows, Cart, NC, USA). In all tests, p < 0.05 was regarded as denoting statistical significance.

RESULTS:

Simple regression analysis revealed a significantly negative correlation between the brachial ankle pulse wave velocity (baPWV) and the serum adiponectin level (r = -0.43, p = 0.003).Stepwise multiple regression analysis revealed the serum adiponectin level and age as major factors determining the baPWV.To analyze the relationship between the serum levels of adiponectin and various parameters of atherosclerosis, the serum adiponectin levels in the patients were divided into tertiles, low group, medium group, and high group.Observation of the changes of the baPWV over one year revealed that the value increased significantly in the low group as compared with that in the patients with values in the high group and medium group.None of the cases with serum adiponectin levels in the medium group and high group developed cardiovascular disease, while one patient each with the serum adiponectin level in the low group died of acute myocardial infarction, developed angina pectoris, and developed cerebral infarction.

CONCLUSIONS:

The results of this study indicate that serum adiponectin are important factors determining the rate of progression of atherosclerosis in chronic hemodialysis patients.

CHLAMYDIA PNEUMONIAE SEROPOSITIVITY IS RELATED TO INCIDENCE OF CARDIOVASCULAR EVENTS IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Chronic infections have been considered a non traditional cardiovascular risk factor in patients undergoing hemodialysis (HD). To date, Chlamydia Pneumoniae (CP) is the most studied infectious agent implicated in promoting atherosclerosis. CP is a gram-negative obligate intracellular bacterium, which has been detected in atheromatous plaques. CP seropositivity has been related to progression of carotid atherosclerosis and ischemic heart disease in HD. However, the association between CP seropositivity and incidence of cardiovascular disease (CVD) was also reported non significant, after adjustment for age and traditional risk factors. So, it is now debated whether CP infection and seropositivity are causal factors of atherosclerosis in HD. Furthermore, the biological basis of the relationship between CP chronic infection and the development of atherosclerosis is quite obscure as yet. The aim of our study is to evaluate, in a group of patients undergoing HD, the relationship among CP seropositivity, global cardiovascular risk and inflammation.

METHODS:

44 patients (age 68,5 ± 12,6 yrs, m/f: 29/15) on regular chronic HD (>3 months) were enrolled. Global absolute Cardiovascular Risk (GCR) was assessed using the validate risk charts of the italian CUORE Project, which evaluate risk factors and categorize the 10-yrs GCR in six classes (scored from 1 to 6: < 5%, 5-9%, 10-14%, 15-19%, 20-29%, > or = 30%). The factors considered were: age, gender, smoking habit, diabetes, systolic blood pressure and serum cholesterol. CP chronic infection was diagnosed by the presence of serum anti-CP IgA and/or IgG (ELISA test). Inflammation was assessed by measurement of erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) serum levels by a high sensitivity enzyme-linked method. The incidence of cardiovascular events, during a 12 months follow-up, was also recorded.

RESULTS:

19/44 patients (43%) resulted seropositive for CP (IgA and/or IgG). Seropositive patients (CP+) were older than seronegative (CP-) (73.4±7.9 vs 64.7±14.3 yrs, p<0.05), while there were no significant differences in gender, CRP (CP+ 1.58±2.8 vs CP- 0.77±1.0 mg/dl, ns) and ESR (CP+ 52.74±29.2 vs CP- 50.92±28.1 mm/h, ns). GCR was also not different between CP+ and CP- (3.0±1.3 vs 2.6±1.5, respectively).During the follow-up, 14 cardiovascular events occurred and the incidence of CVD was significantly higher in CP+ (10 events/19 CP+ vs 4 events/25 CP-, Fisher's test: p<0.05). Multivariate linear regression analysis, adjusted for gender, age and CRP, demonstrated that incidence of CVD was independently correlated with higher GCR and with higher titer of anti-CP IgG (R² = 0.42, p<0.001 and R²=0.17, p<0.05, respectively).

CONCLUSIONS:

CP seropositivity is associated to a higher incidence of CVD, even after adjustment for traditional risk factors. So, the presence of CP should be considered as a factor potentially affecting the cardiovascular risk in HD. However, CP infection seems not to be related to inflammation, other pathogenic mechanisms should be hypothesized.

PREDICTING SUDDEN CARDIAC DEATH IN ESRD PATIENTS: POTENTIAL ROLE OF MICROVOLT T WAVE ALTERNANS

Abstract

INTRODUCTION AND AIMS:

Sudden cardiac death (SCD) is common in end stage renal disease (ESRD) patients and is significantly associated with uraemic cardiomyopathy (left ventricular hypertrophy, systolic dysfunction, or dilation on cardiac imaging). Identification of patients at high risk of SCD is difficult. Microvolt T wave alternans (MTWA) is a new, non invasive method of detecting variability in ECG T wave morphology and is promising for risk stratifying heart failure patients for ventricular arrhythmias (between 55-70% have abnormal MTWA). Five percent of healthy subjects have abnormal results. We performed MTWA testing in ESRD patients to determine the prevalence of n abnormal result.

METHODS:

154 ESRD patients (86 haemodialysis, examined 24 hours after end of last HD session; 16 peritoneal dialysis; 52 stage 5 CKD not receiving renal replacement therapy) underwent assessment including ECG, cardiac MRI and MTWA exercise testing. MTWA results were classified as "negative" or "abnormal" based on previously published reports.

RESULTS:

85 patients (53.5%) had abnormal results. This was significantly associated with past history of ischemic heart disease (11.6% negative vs. 31.8% abnormal; p=0.003), cerebrovascular disease (4.3% vs. 22.4%; p=0.001) and peripheral vascular disease (5.8% vs. 29.4% p<0.0001). There was also a significant difference in resting ECG with ischaemic abnormalities (20.9% negative vs. 43.5% abnormal; p=0.004). There was no significant difference between ejection fraction (63.8% negative vs. 61.1% abnormal; p=0.28). However, LV mass (86.9g/m²negative vs. 100.1 g/m²abnormal; p=0.04), end diastolic (60.0 ml/m² vs 74.5ml/m²) and end systolic (22.9ml/m² vs. 33.2 ml/m²; p=0.03) volumes were significantly higher in patients with abnormal MTWA results.

CONCLUSIONS:

Patients with ESRD have a high prevalence of abnormal MTWA result. Despite normal LV function, this is similar to heart failure patients with normal renal function and is significantly higher than healthy subjects. Abnormal MTWA result is significantly associated with past history of macrovascular (coronary, cerebral, and peripheral) disease, and myocardial structural changes of uraemic cardiomyopathy (higher myocardial mass and LV dilation). The potential predictive role of MTWA in ESRD patients, especially for sudden cardiac death, remains to be assessed.

CORONARY ARTERY CALCIFICATION AND ITS RISK FACTORS IN DIALYSIS PATIENTS WITH LOW OR HIGH TURNOVER BONE DISEASE

Abstract

INTRODUCTION AND AIMS:

The increased cardiovascular mortality observed in dialysis patients could not be only explained by the traditional risk factors present in that population. Calcium and phosphate metabolism alterations are associated with changes in parathyroid hormone secretion and bone disease, and their role in coronary artery calcification (CAC) remains uncertain.The aim of this study was to evaluate CAC and its risk factors in dialysis patients with low or high turnover bone disease diagnosed by bone histomorphometry.

METHODS:

Hemodialysis patients who had been concomitantly submitted to coronary tomography and bone biopsy were retrospectively studied. Sixty-two age- and gender-matched patients were selected according to their bone histomorphometric diagnose: adynamic (ABD) or hyperparathyroid (HPBD) bone disease. ABD (n=31; 44.7±10.6 yrs; 15F/16M) and HPBD (n=31; 42.8 ± 12 yrs; 15F/16M) patients had been submitted to laboratorial evaluation for mineral metabolism, inflammation and lipid profile. Framinghan risk and body mass index (BMI) were calculated for each patient.

RESULTS:

The demographic, laboratorial and coronary tomography parameters of ABD and HPBD patients are shown in the Table. Regarding the lipid profile, there was no difference between both groups. In both groups we found that age and Framingham risk were positively related to CAC, but in the ABD group there was a negative correlation between trabecular thickness and CAC and in the HPBD group there was a positive correlation between alkaline phosphatase and CAC.

CONCLUSIONS:

In dialysis patients, there is no difference between low and high turnover bone disease, regarding the prevalence and the severity of CAC, but probably, distinct physiopatological mecanisms are implicated.

INTRADIALYTIC CHANGES IN ARTERIAL COMPLIANCE AND CARDIOVASCULAR MORTALITY OF MAINTENANCE HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Arterial stiffness is an established predictor of cardiovascular (CV) mortality in ESRD patients. Effect of hemodialysis procedure (HD) on arterial compliance has been revealed in several studies. This study aimed to elucidate whether acute changes in arterial compliance due to HD influence CV death rate.

METHODS:

Sixty-eight patients (31 M and 37 F), aged 56.2±13.7 years, hemodialyzed for 0.3-15.7 years were studied between February and April 2003. Arterial compliance was assessed non-invasively from blood pressure waveform with use of HDI/Pulse Wave CR-2000 Research Cardiovascular Profiling System: prior to, 1 hour into, and following completion of a single HD. Large (C1) and small artery (C2) compliance indices, as well as blood pressures and pulse rate (PR) were automatically estimated. Serum cholesterol and CRP concentrations were measured before HD.Changes in C1 subsequent to HD were calculated as ΔC1_1h=C1_{after 1h of HD}-C1_{before HD} or ΔC1=C1_{after HD}-C1_{before HD}. Changes in C2 and other hemodynamic parameters were assessed likewise. Hierarchical forward Cox hazard regression analysis was applied to check for associations between CV mortality (death due to heart attack, stroke, heart failure or peripheral vascular disease) and traditional risk factors (age, sex, history of CV events, history of CV events in father at age <55 y or mother at age <65 y, diabetes and smoking status, BMI, serum cholesterol), as well as vascular access type, spKt/V, dialysis therapy duration, serum CRP, and pre- and post-HD levels and intradialytic changes in hemodynamic parameters.

RESULTS:

Till June 1^st 2008 five patients were transplanted and 16 remained alive on HD. Out of 47 deaths 29 were due to CV complications. The mean time of survival or until transplant was 942±708 days. The risk of a CV death was augmented by older age, diabetes, history of CV events and higher CRP, whilst it decreased with higher BMI, and increase (or reduced drop) in PR and C2 1 hour into HD (table).

CONCLUSIONS:

Intradialytic decrease in small artery compliance and no rise of pulse rate seem to increase (or predict) the risk of cardiovascular death in maintenance hemodialysis patients. These findings may be useful in development of more accurate cardiovascular risk screening procedures in this population.

EFFECTS OF SIMVASTATIN ON PERIPHERAL BLOOD MONOCYTE SURFACE MARKERS OF ACTIVATION IN CHRONIC HAEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Increasing evidence suggests a key role for monocyte activation in the development and progression of the atherogenetic process. The aim of the present report was to investigate the probable effects of simvastatin treatment on peripheral blood monocyte (PBM) surface markers of activation in chronic haemodialysis (HD) patients.

METHODS:

Eighteen hyperlipidaemic (LDL≥ 130mg/dL) HD patients (9 male, mean age 62±11 years, mean HD duration 71±67 months) received 10mg of simvastatin per day for 6 months. PBM surface expression of CD11b, CD14, CD16, CD62L and CD64 were determined with the use of flow cytometry at baseline and at 3- and 6-months after the initiation of simvastatin treatment.

RESULTS:

At 3 months, a significant decrease in serum total cholesterol (p<0.001), LDL cholesterol (p<0.001) and triglyceride levels (p=0.03) and a concomittant significant reduction in the percentage of CD16+ monocytes (p=0.03) were observed, compared to baseline.

At 6 months, lipid levels remained significantly reduced, not being however further decreased while a significant reduction in monocyte CD14 expression was noted (p<0.001), as well as an apparent, although statistically not significant, increase in monocyte CD62L and CD64 expression, compared with baseline.

CONCLUSIONS:

In hypelipidaemic HD patients, a low-dose 6-month simvastatin treatment appears to influence the expression of PBM surface activation markers towards a less pro-inflammatory phenotype. These actions were preceded by the statin lipid-lowering effects and may represent one of the multiple pathways through which statins exert their anti-atherogenic effects.

SPIRONOLACTONE IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS, IMPROVES CARDIAC FUNCTION

Abstract

INTRODUCTION AND AIMS:

Cardiovascular disease is recognized as the predominant cause of death in patient with chronic kidney disease. Use of spironolactone in conjunction with an ACEI or ARB reduce the risk of cardiac mortality and morbidity in patients with normal or slightly decreased renal function. Since dialysis patients are prone to hyperkalemia, is a known side effect of spironolactone, this treatment has not been used in this population. We performed a study to assess whether low-dose spironolactone (3 x 25 mg/week) could be administered in Continuous Ambulatory Peritoneal Dialysis patients with moderate to severe heart failure to improve cardiovascular function without inducing hyperkalemia.

METHODS:

In a triple blinded, randomized, placebo controlled study, we enrolled eighteen patients who where under peritoneal dialysis treatment with moderate to severe heart failure and left ventricle ejection fraction of not more than 45 percent and use of ACEI and serum potassium level less than 5.5 meq/l. One group of nine patients received 3 x 25mg/week of spironolactone and another group received placebo within six months. Echocardiography was also performed for both group, at the beginning and the end of study, to assess ejection fraction. Serum potassium was measured every four weeks.

RESULTS:

The mean of Ejection Fraction increased more in spironolactone group during the time (p=0.002) than in placebo group during the time (p=0.4).There was no significant change in serum potassium between two group (p>0.05) but there was a significant difference in mortality between two group (p=0.03).

CONCLUSIONS:

This study show that administration of spironolactone in continuous ambulatory peritoneal dialysis patients with severe heart failure, substantially improve their cardiac function and decreases mortality without development of severe hyperkalemia.

AORTIC CALCIFICATION, SERUM FETUIN-A AND INFLAMMATION IN CHRONIC HAEMODIALYSIS PATIENTS: IMPACT ON MORTALITY

Abstract

INTRODUCTION AND AIMS:

Vascular calcification is a common complication of end-stage renal disease and is associated with the increased mortality observed in this patient population. The underlying mechanisms are not yet well understood but recent evidence suggests that dysregulation of calcification inhibitors and inflammation may be important determinants. The aim of this prospective study was to evaluate the associations between aortic calcification, serum fetuin-A and inflammation and their impact on mortality in chronic haemodialysis (HD) patients.

METHODS:

Eighty-five patients (45 males, mean age 58±17 years, mean HD duration 61±62 months) were included. Fourteen patients (16.5%) had diabetes and 21 (24.7%) had a history of cardiovascular disease (CVD). The abdominal aorta was examined in all patients at baseline on consecutive non-contrast computed tomographic scans and aortic calcification index (ACI) was calculated as the proportion of aortic circumference covered by calcification. High sensitivity CRP (hsCRP) was measured by nephelometry. Serum fetuin-A and IL-6 levels were determined by ELISA. The patients were followed up for a period of 25.3±13 months.

RESULTS:

In univariate analyses, ACI was positively correlated with age (p<0.001), HD duration (p<0.001), smoking (p=0.032), hsCRP (p=0.003) and IL-6 levels (p<0.001) and negatively with serum albumin (p=0.004). iPTH (p=0.053) and fetuin-A (p<0.001). After controlling for all other variables, age (p<0.001), HD duration (p=0.044) and serum fetuin-A (p=0.001) remained significant independent predictors of ACI values. During follow-up, 24 patients died, mostly due to CVD events (54.2%). Compared to survivors, non-survivors were older (53.1±18.0 vs 70.6±7.9 years, p<0.001) and had significantly higher ACI (45.1±36 vs 77.8±21%, p<0.001), lower fetuin-A (0.447±0.061 vs 0.410±0.089 g/L, p=0.014), higher hsCRP levels (5.3±4.2 vs 14.0±9.8 mg/L, p<0.001) and higher IL-6 (6.5±5.9 vs 12.5 ±10.2 pg/ml, p=0.004). Kaplan-Meier survival curves differed significantly between patients with ACI <50% and ≥50% (p=0.003). In addition, compared to patients with fetuin-A, hsCRP and IL-6 levels <median, a higher mortality rate was observed in patients with fetuin-A, hsCRP and IL-6 levels ≥median (p=0.019, p=0.018 and p=0.053 respectively). In Cox-regression analysis mortality correlated with age (p=0.001), serum albumin (p=0.01), fibrinogen (p=0.002), ACI (p=0.002), serum fetuin-A (p=0.047), hsCRP (p<0.001) and IL-6 (p<0.001). In multivariate analysis only age (p=0.027) and hsCRP (p=0.041) remained independent predictors of mortality.

CONCLUSIONS:

In chronic haemodialysis patients, aortic calcification is associated with serum fetuin-A levels and inflammation and has an impact on outcome. However, inflammatory markers appeared as better predictors of mortality in this high-risk patient population.

INFERIOR VENA CAVA DIAMETER AS A BLOOD PRESSURE-INDEPENDENT DETERMINANT OF LEFT VENTRICULAR MASS INDEX AND ARTERIAL STIFFNESS IN HAEMODIALYSIS

Abstract

INTRODUCTION AND AIMS:

Although volume status contributes toward cardiovascular target organ changes in chronic renal failure, the relative contribution of blood pressure (BP)-dependent and -independent mechanisms has not been determined. This study assessed whether inferior vena cava diameter (IVCD), an index of volume status was associated with left ventricular mass (LVM) and geometry and large artery dysfunction independent of multiple pre- and post- dialysis BP measurements and 24-hour BP in 94 non-diabetic patients receiving maintenance haemodialysis (MHD) for an average of ~49 (3-300) months.

METHODS:

Pulse wave analysis (PWA) performed at the carotid, femoral and radial artery was employed to determine carotid-femoral pulse wave velocity (PWV) and central augmentation index (AIc). Echocardiography was performed to determine LVM which was indexed to body surface area (LVMI) and LV geometry and IVCD was determined using ultrasound techniques.

RESULTS:

After adjustments for a number of potential confounders (such as age, sex, body mass index, number of antihypertensive agents used and smoking) as well as the average of pre- and post-dialysis systolic BP (SBP) values or 24-hour SBP, IVCD was independently associated with LVMI (partial r adjusted for average dialysis SBP=0.27, p=0.014; partial r adjusted for 24-hour SBP=0.29, p=0.013), and LV mean wall thickness (p<0.01), but not with either LV relative wall thickness (p=0.18), or LV end diastolic diameter (p=0.88). Moreover, after adjustments for a number of potential confounders as well as the average of pre- and post-dialysis systolic BP (SBP) values or 24-hour SBP, an association between IVCD and AIc (partial r adjusted for average dialysis SBP=0.21, p<0.05), but not PWV was noted.

CONCLUSIONS:

These data support the notion that in patients receiving HD, volume-overload produces effects on cardiovascular target organs that are not predicted by BP effects alone.

EFFECT OF TREATMENT OF HYPERURICEMIA WITH ALLOPURINOL ON ENDOTHELIAL FUNCTION IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Studies have found that hyperuricemia is associated with increased mortality and development of hypertension and cardiovascular. We recent showed that uric acid (UA) was associated with flow-mediated dilatation (FMD), a marker of endothelial function, in peritoneal dialysis (PD) patients. In the present study we are performing a control study to explore the impact of UA management on FMD in a group of PD patients.

METHODS:

A total of 113 (75 hyperuricemia and 38 normal uric acid) PD patients were included. Hyperuricemia individuals were divided into test (38 individuals) and control (37 individuals) groups randomly. Patients in test group with serum uric acid levels≥420μmol/L (19 women, 19 men) were treated with allopurinol 100mg/Bid for one month. Individuals in control and normal uric acid groups were not treated with allopurinol. Patients and normal uric acid subjects were examined at baseline and after one month of therapy in test group. FMD was measured by sonography.

RESULTS:

In the test group, uric acid levels (p < 0.01) and flow-mediated dilation (p < 0.05) improved significantly whereas no significant changes in the control and normal uric acid groups were recorded (p > 0.05). There were no significant differences among the three groups regarding the antihypertensive agents, lipid lowering medications or other laboratory parameters.

CONCLUSIONS:

Treatment of hyperuricemia significantly improves FMD in PD patients.

HYPERVOLEMIA RATHER THAN ARTERIAL CALCIFICATION AND EXTRACORONARY ATHEROSCLEROSIS. IS THE MAIN DETERMINANT OF PULSE PRESSURE IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Pulse pressure has been reported as an independent predictor of cardiovascular mortality in hemodialysis (HD) patients. According to studies mostly done on nonuremic populations, pulse pressure represents arterial stiffness and function of the large conduit arteries. In this study, we aimed to investigate association between pulse pressure and vascular structural changes such as atherosclerosis and arterial calcifications in HD patients.

METHODS:

In this cross-sectional study, 108 chronic hemodialysis patients (49 male, 59 female, mean age: 46 ± 13 years) were included. Biochemical analysis, echocardiographic examination and high-resolution carotid Doppler examinations were done. Aortic wall and coronary artery calcifications were measured with electron beam computed tomography. Degree of carotid artery stenosis was measured from four different sites (communis, bulbus, interna and externa) in both of the carotid arteries. Carotid plaque scores were calculated by summing the degree of stenosis measured from all locations.

RESULTS:

Pulse pressure was strongly correlated with systolic and diastolic blood pressure, left ventricular mass index (r:0.58), left ventricle end diastolic diameter (r:0.38) and weakly correlated with aortic wall calcification score (r:0.26) and carotid plaque score (r:0.27), but not with coronary artery calcification score. Patients with carotid plaque (n:60) had higher pulse pressure than patients without plaque (n:44) (50±16 mmHg vs 44±14 mmHg, p=0.05). Patients were divided into three groups according to aortic wall calcification score. Pulse pressure was significantly higher in patients with higher aortic wall calcification (54±16 mmHg) than patients with lower aortic wall calcification (44±15 mmHg, p=0.04). However on multivariate linear regression analysis for pulse pressure only significant factor retained was left ventricle end diastolic diameter.

CONCLUSIONS:

Pulse pressure was weakly associated with large vessel calcification and atherosclerosis in hemodialysis patients. The bulk of the effect on pulse pressure was due to hypervolemia.

RISK FACTORS FOR DE NOVO ARTERIAL STIFFNESS IN DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Arterial stiffness (AS) is a strong independent predictor of overall and cardiovascular mortality, particular in chronic kidney disease and end stage renal disease patients. The objective of this study was to determine the risk factors for the de novo AS in the long term dialysis patients.

METHODS:

One hundred and forty long term dialysis patients were studied in March 2007. Cardio-ankle vascular index (CAVI) was measured for each dialysis patient. The CAVI value of 9 was defined as the threshold value for AS according to the manufacturer's definition. Then, eighty-one dialysis patients already had AS (CAVI > 9) were excluded and fifty-nine dialysis patients without AS were recruited and followed up for one year from March 2007 to February 2008. One year later, CAVI was measured, and CAVI > 9 was defined as de novo AS. The initial baseline characteristics (age, height, body weight, body mass index, waist circumference, gender, smoking history causes of ESRD, dialysis model, duration for dialysis, pre-existing cardiovascular disease, peripheral arterial disease, medications with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, hypoglycemia agents, lipid-lowering agents, Vitamin D, dose of CaCO3) and laboratory parameters (albumin, glucose, HbA1C, cholesterol, HDL, triglyceride, uric acid, total calcium, phosphate, and Ca x PO4 products, intact parathyroid hormone, C-reactive protein, homocysteine, hematocrit) between long term dialysis patients with and without de novo AS were analyzed.

RESULTS:

Twenty-two dialysis patients had de novo AS during this one year follow up. The incidence rate was 37.3%. Age of dialysis patients with de novo AS was significantly older than that of dialysis patients without de novo AS (60.23 ± 12.48 years vs 52.81 ± 13.90 years, P =0.044). Serum phosphate (5.69 ± 1.22 mg/dl vs 4.78 ±1.12 mg/dl, P=0.005) and Ca x PO4 products (53.01 ± 13.48 mg²/dl²vs43.54 ± 10.72 mg²/dl², P=0.004) of dialysis patients with de novo AS were significantly higher than those of dialysis patients without de novo AS. Hematocrit of dialysis patients with de novo AS was significantly lower than that of dialysis patients without de novo AS (30.15 ± 4.36 % vs 32.33 ± 3.48 %, P=0.038). Multivariate logistic regression analysis showed that age (adjusted odds ratio=1.064, p=0.022) and serum phosphate (adjusted odds ratio=2.193, p=0.008) of initial dialysis were the significantly independent determinants of dialysis patients with de novo AS.

CONCLUSIONS:

Age and serum phosphate are significantly independent risk factors for de novo AS in dialysis patients.

EVALUATION OF ARTERIOSCLEROSIS IN HEMODIALYSIS PATIENTS USING STIFFNESS PARAMETER BETA: A NEW INDEX OF VASCULAR WALL STIFFNESS

Abstract

INTRODUCTION AND AIMS:

Cardiovascular and cerebrovascular diseases are major cause of mortality among patients with end-stage renal disease, and incidence of vascular complications is significantly higher in haemodialysis(HD) patients. It is well known that the carotid findings reflects systemic arterial sclerosis. Measurement of intima-media thickness(IMT) by a carotid echo has been generally used to evaluate arteriosclerosis. In this study, to evaluate arteriosclerosis in maintenance HD patients, stiffness parameter β (SP-β, a new parameter which reflects systemic atherosclerosis) and pulse wave velocity (PWV) were measured in addition to IMT. Other chemical parameters were also measured.

METHODS:

Sixty-six patients (34 male,32 female;mean age 64±12)on maintenance HD treatments were recruited into our study from our HD units. These patients consisted of 22 diabetic patients and 44 non-diabetic patients. We measured SP-β and PWV to evaluate the arteriosclerotic status in each patient. We measured SP-β, which represented the mechanical properties in the arterial wall, with an ultrasonic phase-locked echo-tracking system (ProSound SSD II 6500, Aloka Co. Ltd.) that allows noninvasive and continuous transcutaneous measurement of the arteial diametere and blood pressure. SP-β reversely relates to distensibility, therefore the higher SP-β values mean grater arterial wall stiffness. We investigated the associations between the SP-β and PWV with plasma total cholesterol, triglyceride, low-density lipoprotein cholesterol, serum calcium, phosphorus, parathyloid hormone, age and duration of dialysis. Values were expressed as mean±SD. Significant differences between two groups were assessed using the Mann-Whitney U-test. Values of p<0.05 were regarded as significant.

RESULTS:

SP-β did not correlate with total cholesterol, triglyceride, low-density lipoprotein cholesterol, serum calcium, phosphorus, parathyloid hormone and duration of dialysis. Age, IMT, PWV positively correlated with SP-β(y=0.96x+49.82, r²=0.18, p<0.01; y=0.06x+0.14, r²=0.40, p<0.01; y=31.03x+1514.07, r²=0.09, p<0.05, respectively). There was no significant difference in SP-β from 15.8±7.2(diabetic patients) to 14.3±4.6(non-diabetic patients), although PWV was significantly higher in diabetic patients(2300±455cm/sec) than non-diabetic patients(1805±511cm/sec).

CONCLUSIONS:

In the present study, age, IMT, and PWV correlated with SP-β in maintenance HD patients. It suggested the reasonability of SP-β as a new index of vascular wall stiffness. Although there was no significant difference between diabetic and non-diabetic patients in SP-β, PWV was significantly higher in diabetic patients than non-diabetics. It may reflect that some underlying factors such as advanced systemic arteriosclerosis in diabetic patients can accelerate PWV.

DIFFERENCES IN CLINICAL CHARACTERISTICS BETWEEN AORTIC AND MITRAL VALVE CALCIFICATION IN HEMODIALYSIS

Abstract

INTRODUCTION AND AIMS:

Heart valve calcification is frequently observed in patients on hemodialysis (HD), but there remains a question whether calcification of aortic and mitral valves arises from similar pathogenesis. We evaluated risk factors and prognostic value for all-cause mortality for aortic and mitral valve calcification in HD patients.

METHODS:

We evaluated aortic and mitral valve calcification by echocardiography in patients treated with HD three times a week for more than one year. We compared the clinical parameters between the patients with and without aortic and mitral valve calcification. In addition, we analyzed the relationship of valve calcification with all-cause mortality.

RESULTS:

Of 112 patients including 77 males and 35 females (age 67 ± 10 years, duration on HD 95 ± 67 months), calcification of aortic and mitral valves was observed in 84 (75.0%) and 58 patients (51.7%), respectively. Fifty patients (44.6%) showed calcification of both valves. The patients with aortic valve calcification showed significantly higher age (69 ± 8 vs 62 ± 13 years, P = 0.01), lower serum albumin (3.6 ± 0.2 vs 3.8 ± 0.2 g/dL, P = 0.009), higher serum calcium (9.1 ± 0.8 vs 8.7 ± 0.6 mg/dL, P = 0.03), lower total cholesterol (148 ± 33 vs 162 ± 34 mg/dL, P = 0.03), and higher high sensitive-C-reactive protein (hs-CRP; 0.29 ± 0.38 vs 0.13 ± 0.22 mg/dL, P = 0.003) compared with those without aortic valve calcification. On the other hand, those with mitral valve calcification showed higher age (70 ± 9 vs 65 ± 11 years, P = 0.03), higher hs-CRP (0.30 ± 0.33 vs 0.19 ± 0.38 mg/dL, P = 0.01), and higher serum β₂-microglobulin (β₂M; 30.1 ± 5.6 vs 27.2 ± 5.1 μg/mL, P = 0.007) compared with those without mitral valve calcification. Serum β₂M was independently associated with mitral valve calcification in multivariate analysis [odds ratio 1.10 (95%CI 1.01-1.20), P = 0.01]. During the follow-up period of 30.8 ± 8.6 months, 22 patients (19.6%) died. Non-survivors showed significantly higher age (72 ± 6 vs 66 ± 10 years, P = 0.01), lower serum albumin (3.5 ± 0.3 vs 3.7 ± 0.2 g/dL, P = 0.01), higher triglyceride (123 ± 96 vs 82 ± 41 mg/dL, P = 0.02), and higher prevalence of mitral valve calcification (77.2% vs 45.5%, P = 0.008) compared with survivors. However, the prevalence of aortic valve calcification was comparable between non-survivors and survivors (81.8% vs 73.3%, P = 0.41). The survival curve estimated by Kaplan-Meier method and a log-rank test showed that the patients with mitral valve calcification had a significantly higher all-cause mortality compared with those without mitral valve calcification (P = 0.006).

CONCLUSIONS:

Our results suggested that aortic and mitral valve calcification have different characteristics. In particular, the association between mitral valve calcification and serum β₂M was notable. In addition, mitral valve calcification, not aortic valve calcification, could predict all-cause mortality.

HAEMODIALYSIS ALTERS ATRIAL EXCITABILITY: A COMBINED COMPUTATIONAL AND P WAVE ANALYSIS

Abstract

INTRODUCTION AND AIMS:

Atrial fibrillation (AF) prevalence is high in end stage renal disease (ESRD) and haemodialysis (HD) session may trigger paroxysmal AF episodes. AF onset is mainly determined by two phenomena: a) structural and electrical atrial remodelling b) extrasystolic firing from atrial ectopic foci. Structural remodeling is often present in ESRD patients and supraventricular ectopic beat occurrence increases in the last stage of the HD session. There are two electrophysiological aspects of electrical atrial remodeling: a) shortening of atrial cell refractory period b) slowing of intra-atrial electrical conduction. The ECG P wave duration (PWD) reflects the atrial conduction velocity, whereas through computational analysis the effects of electrolyte variations on action potential (AP) morphology and duration can be quantified. Our aim was to highlight the HD-induced acute electrical remodeling potentially leading to AF onset.

METHODS:

In 16 (age 58

±

19) ESRD patients data were obtained before and after HD sessions. PWD was measured by a signal averaged ECG, as an expression of intra-atrial conduction velocity. Heart rate, Na⁺, K⁺ and Ca²⁺ plasma concentrations were measured. The Courtemanche computational model of human atrial myocyte was used to simulate the atrial AP. The effects of HD were analysed by imposing extracellular electrolyte concentrations and heart rate to the average values measured in vivo. Maximum upstroke velocity (Vmax), AP duration (APD) and the atrial effective refractory period (ERP) were computed.

RESULTS:

HD induced changes in electrolyte concentrations: K⁺ plasma concentration decreased (from 5.0±0.6 to 3.8±0.4 mmol/L, p<0.001), Na⁺and Ca²⁺concentrations increased (from 140±4 to 142±3 mmol/L, p<0.05, and from 1.17±0.09 to 1.30±0.07 mmol/L, p<0.001, respectively). Heart rate was unchanged (from 74±12 to 73±13 bpm, NS).

PWD slightly but systematically increased after dialysis (p<0.01), indicating a HD-induced slowing of intra-atrial conduction. Increases of PWD were significantly inversely correlated with variations of K⁺ (R= 0.73,p< 0.01). The model-based analysis indicated at the end of HD a reduction in Vmax coherent with experimental observations on PWD. Moreover, while APD slightly increased at the end of HD, ERP decreased by 14 ms.

CONCLUSIONS:

This analysis suggests that during HD session the changes of plasma ionic concentrations may lead to modifications of atrial electrophysiology that can favourite AF onset, namely a decrease of atrial conduction velocity (increased PWD) and a decrease of atrial ERP.

DISCLOSURE:

The present work was partially funded by Hospal SpA grant to S. Severi

INCREASING CARDIAC TROPONIN T LEVELS AFTER THE INITIATION OF HEMODIALYSIS ARE ASSOCIATED WITH DIALYSIS-RELATED LEFT VENTRICULAR HYPERTROPHY

Abstract

INTRODUCTION AND AIMS:

Elevated serum cardiac troponin T levels (cTnT) and the worsening of left ventricular hypertrophy (LVH) are related to mortality in hemodialysis (HD) patients. However, there are few data on their link in the early stage of HD treatment. This study was conducted to clarify the association after starting HD treatment.

METHODS:

Among 76 patients undergoing HD at our hemodialysis clinic, 21 patients who were measured cTnT at the initial stage of HD and followed up over 4 years, were enrolled. For each patient, routine laboratory tests, cTnT and echocardiographic study were performed annually.

RESULTS:

Eight patients with initially-positive cTnT levels (>=0.04 ng/ml) had higher prevalence of diabetes and plasma brain natriuretic peptide (BNP) levels. Among 13 patients with initially-undetectable cTnT levels, elevation of cTnT levels were observed in 6 patients during the follow-up periods. In this group, higher pulse pressure, age, prevalence of diabetes, BNP, C-reactive protein and lower albumin levels were observed. Additionally, we also observed an increase in left ventricular mass index (LVMI). Surprisingly, in patients with persistently-negative cTnT levels, LVMI had been decreasing throughout the follow-up periods. The change in LVMI was significantly higher in TnT-positive group than TnT-negative group (29% vs -10%, p<0.05).

CONCLUSIONS:

An increase in serum cardiac troponin T levels after the initiation of hemodialysis treatment is associated with progression of left ventricular hypertrophy.

TRADITIONAL CARDIOVASCULAR RISK FACTORS AND CARDIOVASCULAR MORTALITY IN HAEMODYALISIS PATIENTS: 5-YEAR FOLLOW-UP ANALYSIS

Abstract

INTRODUCTION AND AIMS:

The prevalence of traditional cardiovascular (CV) risk factors among haemodyalisis (HD) patients is very high, but data regarding whether traditional risk factors are valid predictors of CV disease in HD patients are controversial. The aim of the study was to elucidate the relevance of traditional CV risk factors for CV mortality in HD patients, together with predialysis nephrological care duration (PNCD) and CV disease before starting HD (prior CV disease).

METHODS:

A total of 261 prevalent HD patients (mean age at beginning of HD 49.69±15.59 years, mean HD vintage 99.54±72.15 months, diabetes 17.2%) were prospectively followed up for 60 months and all-cause and cardiovascular mortality were registered. We examined several traditional CV risk factors according to the currently recommend goals:systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), total cholesterol, triglycerides, HDL-high-density lipoprotein, LDL-low-density lipoprotein, smoking, BMI-body mass index, presence of diabetes and left ventricular hypertrophy (LVH) by echocardiography. PDNC was quantified as the time-interval between the start of regular care and the day of first HD. Prior CVdisease was defined by a history of myocardial infarction or cerebral infarction or presence of congestive heart failure.

RESULTS:

During the 5-year follow-up, 117 out of 261 patients (44.8%) had died, most from CV diseases (63.2%). Among the 261 patients prior CVdisease had 46.4% and PNCD<12 months had 66%. Both, Kaplan-Meier and univariate Cox analysis showed that age, presence of diabetes, prior CVdisease, PNCD<12vs>12months, PP>60vs≤60mmHg and LVH (>131g/m2 for men and >100g/m2 for women), were predictors of all-cause and CV mortality. DBP<70vs70-90mmHg was a predictor of all-cause mortality, and SBP>150vs<130mmHg was a predictor of CV mortality. Interestingly, neither BMI (BMI<23vs≥23 kg/m2), nor HDL (<1.03vs>1.03mmol/l), as well as LDL (>3.36vs<3.36), triglycerides (<1.69vs>1.69), and smoking were associated with mortality in the follow-up period. Multivariate Cox regression analysis, adjusted for age, showed that prior CV disease (HR 1.99; 95%CI 1.04-3.81, p=0.037), DBP<70vs70-90mmHg (HR 3.96; 95%CI 2.00-7.83, p=0.000), PP>60vs≤60mmHg (HR 5.92; 95%CI 1.64-21.38, p=0.007) and LVH (HR 2.48; 95%CI 1.09-5.64, p=0.031) were predictors of all-cause mortality, but only prior CVdisease (HR 2.17; 95%CI 1.01-4.68, p=0.048) and PP>60vs<60mmHg (HR 11.76; 95%CI 1.56-88.96, p=0.017) were predictors of CV mortality in HD patients.

CONCLUSIONS:

Traditional CV risk factors before starting HD including a prior CV disease were the strongest predictors of CV mortality in HD patients. In addition, during maintenance HD, a unique traditional risk factor - the pulse pressure, was associated with higher CV mortality.

HIGHER VISCERAL FAT AREA IS A RISK FACTOR OF CARDIOVASCULAR DISEASE IN CHRONIC DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

The risk of cardiovascular disease is substantially high in dialysis patients. The risk factors for cardiovascular disease in dialysis patients include age, duration of dialysis, diabetes mellitus and hyperphosphatemia. However it is not clear cardiovascular disease is associated with visceral fat area in dialysis patients. We investigated the relationship among visceral fat area, several clinical and biochemical parameters and anamnesis of cardiovascular complication in chronic dialysis patients.

METHODS:

In the Japanese guidelines of metabolic syndrome, equivalent for over 100cm²of visceral fat area is an essential condition.Area of visceral fat was measured using computed tomographic scanning in 94 non-diabetic patients. Patients were divided into two groups according to visceral fat area; those with visceral fat area < 100cm²(Group A) and with > 100cm² (Group B). These patients were subdivided according to duration of dialysis; i.e., less than 5-year (Group A-1, Group B-1) and more than 5-year (Group A-2, Group B-2). The abdominal aortic calcification index (ACI), blood chemistry of lipid and complication of cardiovascular disease were evaluated in these patients.

RESULTS:

Compared to Group A, Group B showed, significantly higher serum levels of triglyceride (96.8±38.1mg/dl vs. 167.6±77.5mg/dl, p<0.001) and significantly lower, high-density lipoprotein-cholesterol levels (52.7±11.9mg/dl vs. 35.7±8.2mg/dl, p<0.001). Group B also showed higher rate of cardiovascular complication. ACI was 31.3±4.5%(Group A-1), 38.1±4.3%(Group A-2), 38.2±7.4%(Group B-1), 53.4±9.0%(Group B-2), suggesting that obese patients with longer duration of dialysis showed severer calcification. The rate of ischemic heart disease in Group B-2 was significantly higher than that in any other groups.

CONCLUSIONS:

This study suggested that the patients with higher visceral fat area might have cardiovascular diseases. Higher visceral fat area can be a contributing risk factor to cardiovascular disease, especially ischemic heart disease in chronic dialysis patients.

THE RELATIONSHIP BETWEEN PREMATURE ATHEROSCLEROSIS AND SERUM ADIPONECTIN AND RESISTIN LEVELS IN CHRONIC RENAL FAILURE PATIENTS

Abstract

INTRODUCTION AND AIMS:

Cardiovascular diseases are the leading cause of morbidity and mortality in chronic renal failure starting from the very early stages of the disease. Recent studies have shown that adipose tissue is a complex organ with pleiotropic functions far beyond the storage of energy. Fat tissue secretes a number of adipokines including adiponectin and resistin which are implicated in the pathogenesis of atherosclerosis. The purpose of this study was to assess the relationship between premature atherosclerosis and serum adiponectin and resistin levels in patients with chronic renal failure (CRF).

METHODS:

The study was performed on 52 nondiabetic patients with stage 3-5 chronic renal failure (35 predialysis + 17 dialysis) and 34 non-uremic controls matched for sex and body mass index. Serum adiponectin and resistin levels were measured by ELISA. Carotid intima-media thickness (IMT), a surrogate of premature atherosclerosis, was measured by high resolution B-mode ultrasonography. C-reactive protein (CRP), albumin, insulin resistance (as assessed by HOMA-R) and other metabolic parameters were determined.

RESULTS:

Serum adiponectin levels (μg/ml) were higher in dialysis and predialysis patients than control patients (33.7±30; 18.8±12.7 and 4.9±2.5, respectively, P=0.0001); however, no statistically significant difference was found between predialysis and dialysis groups. Similarly, serum resistin levels (ng/ml) were found to be higher in dialysis and predialysis patients than control patients (17.7±3; 15.5±3.7 and 8.4±2.8, respectively, P=0.0001); however, no statistically significant difference was found between predialysis and dialysis groups. IMT levels (mm) were higher in dialysis and predialysis patients than control patients (0.75±0.23; 0.78±0.24; and 0.48±0.16, respectively, P=0.0001), however, no significant difference was found between predialysis and dialysis patients. In CRF patients, adiponectin levels showed positive correlations with HOMA-R (r=0.28, P=0.044), creatinine (r=0.27, P=0.05) and negative correlation with GFR (r= -0.29, P=0.034). Resistin levels showed positive correlation with creatinine (r=0.36, P=0.009) and negative correlation with creatinine clearance (r= - 0.33, P=0.017). In the analysis of total cohort, correlations were detected between the levels of IMT and age (r=0.62, P=0.0001), creatinine (r=0.29, P=0.006), creatinine clearance (r= -0.54, P=0.0001), adiponectin (r=0.32, P=0.003), resistin (r=0.45, P=0.0001), CRP (r=0.29, P=0.006) and albumin (r= -0.41, P=0.0001).

CONCLUSIONS:

Adiponectin and resitin levels were increased in both predialytic and dialytic stages of chronic renal failure. The associations between the serum adiponectin and resistin levels and carotid IMT may indicate a potential role of these inflammatory cytokines in the pathogenesis of premature atherosclerosis in chronic renal failure.

THE EFFECT OF DECLINED RESIDUAL RENAL FUNCTION ON ENDOTHELIAL FUNCTION IN CONTINUAL PERITONEAL DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Residual renal function (RRF) is an independent predictor of cardiovascular disease (CVD) in dialysis patient. Although many factors contribute to the pathogenesis of CVD, endothelial dysfunction is considered as a triggering factor. The aim of this study was to evaluate the effect of declined RRF on endothelial function in patients on continuous ambulatory peritoneal dialysis (CAPD).

METHODS:

All the incident PD patients between January 1 and August 1, 2007 in a single center and survived longer than 1 year were included into this retrospective study. RRF was assessed by renal clearance of urea nitrogen (rKt/V). Endothelial function was measured by flow mediated dilatation (FMD). All tests were performed twice: at baseline and the end of the study.

RESULTS:

In total, 47 patients were included and followed-up for a mean of 1 year. They were further divided into group A (stable RRF, n=23) and group B (declined RRF, n=24) according to the changes in rKt/V during the study period. The FMD did not change significantly in group A (8.62±7.52 vs. 8.58±5.89%, P=NS), but decreased significantly in group B (10.28±7.02% to 5.25±2.83%, P<0.001). The total glucose absorption, calcium and uric acid in group B increased significantly as compared with baseline values (P<0.05), while they did not change significantly in group A.

CONCLUSIONS:

This study showed that decline of RRF in incident CAPD patients would lead to worsened endothelial dysfunction, while a stable RRF seemed not affect endothelial function significantly. This study highlighted the justification of protecting RRF in this population.

ASSOCIATION BETWEEN VASCULAR STIFFNESS AND AORTIC CALCIFICATION SCORE IN A COHORT OF INCIDENT PERITONEAL DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Vascular calcifications, increased vascular stiffness and mineral metabolism abnormalities are highly prevalent in dialysis patients and associated with poor outcomes. Data regarding ESRD patients at time of dialysis initiation are relatively limited.In this study we describe a cohort of incident peritoneal dialysis (PD) patients in regards to vascular stiffness, aortic vascular calcification, mineral metabolism abnormalities, peritoneal membrane characteristics and initial adequacy results.

METHODS:

A total of 32 patients were studied in the first week of PD training in 2 peritoneal dialysis programs in Vancouver. Semi-quantitative aorta calcification scores were calculated using plain lateral abdominal X-rays. Carotid-femoral PWV and AIX were measured by SphygmoCor technology. PET and initial adequacy test were performed on the same day 4 weeks after starting PD. Laboratory results were accrued at dialysis commencement.

RESULTS:

The cohort included racially diverse group of adults (50% Caucasian, 59% male, mean age 59 years), 31% were diabetic and 22% had known cardiovascular disease at dialysis commencement. Mean serum phosphate was 1.8 ± 0.1 mmol/l, mean calcium 2.2 mmol/l and median intact PTH was 24.5pmol/L (IQ range 20.7- 41.3).57% of all patients demonstrated some degree of aortic calcification at the starting of dialysis. Dividing tertiles of PWV, factors such as age, diabetes and pulse pressure were associated to higher vascular stiffness. Furthermore reduced arterial compliance was found to be associated to increased calcification scores (p < 0.0001).

Figure 1 shows the association between PWV and tertiles of patients based on aortic calcification score (0, 1-6, >7). Interestingly, within the 3 tertiles of calcification scores, higher phosphate levels were associated with lowest scores. No other significant associations were found between calcification score or arterial stiffness and laboratory, demographic or clinical characteristics.

CONCLUSIONS:

In incident PD patients, 57% demonstrated some degree of calcification of the abdominal aorta. The aortic calcification score was strongly associated with the degree of arterial stiffness measured. Further analysis are needed to better explore the association of lower phosphate levels and higher calcification score. Furthermore, prospective data will be needed to associate these findings with clinical outcomes.

DISCLOSURE:

This project was funded by an unrestricted academic grant from Genzyme.

COMPARISON OF VASCULAR CALCIFICATION SCORES ON THE PLAIN RADIOGRAPH AS A PREDICTOR OF CORONARY ARTERY DISEASE IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Vascular calcification (VC) scores on simple plain radiographic films are known to be associated with coronary artery disease (CAD) and mortality. However, there is no report about the correlation between each VC scores on the plain radiograph of different sites and it is unclear to check every plain radiograph as screening. The present study was designed to find any correlation among VC scores of hands and pelvis, feet and lateral lumbar spine on the plain radiograph. In addition, we aimed to analyze the usefulness of checking all the VC scores with plain radiographs for the assessment of pre-existing CAD.

METHODS:

We recruited a total of 61 hemodialysis (HD) patients (male: 23 patients, diabetes: 28 patients) from Dong-A University dialysis center. We checked plain radiographic films of the pelvis, hands, feet and lateral lumbar spine and evaluated VC scores with previously reported methods. We defined CAD based on myocardial SPECT scan, echocardiography or coronary angiography.

RESULTS:

The mean age of the patients was 57.1 ± 13.0 years and the mean HD duration was 46.8 ± 6.2 months (mean±S.E.). Positive correlations were found between VC scores and the presence of CAD.

In aproximately 30%, patients who had CAD could be missed as not having CAD by single VC scoring method. Patients who showed any one finding among the abdominal aortic calcification scores >4 (total of 24), VC scores of pelvis and hands>2 (total of 8) or arterial media calcification of feet on the plain radiograph had a high sensitivity (94.1%) and a high negative predictive value (96.3%) for the presence of CAD.

CONCLUSIONS:

Every VC score was highly correlated with each other. Combinations of the VC scores on the plain radiographic films of four different sites (pelvis, hands, feet and lateral lumbar spine) are useful screening tests for the presence of CAD in HD patients.

OXIDIZED LDL, ANTIBODIES TO OXIDIZED LDL AND ITS EFFECT ON SURVIVAL OF HAEMODIALYSIS (HD) PATIENTS

Abstract

INTRODUCTION AND AIMS:

Oxidative stress and lipid metabolism disorders belong among the factors participating in early atherosclerosis development in HD patients. Evidence exists that HD patients are exposed to enhanced oxidative stress. Increased oxidative stress combined with chronic inflammation may lead to an increased risk of CVD. Oxidized low density lipoproteins (oxLDL) are oxidatively modified lipoproteins associated with atherosclerosis. These modified particles serve as antigen for antibodies against oxidized LDL (IgoxLDL). Effect of oxLDL, IgoxLDL and routine lipid parameters on survival of HD patients was investigated.

METHODS:

Blood samples were collected from 176 chronically haemodialysed patients (70 females and 106 males with mean age ± SD = 66.4 ± 10.63 years) and 73 men with normal kidney function (mean age ± SD = 48.15 ± 5.78 years) who served as controls. Mercodia OxLDL and Biomedica oLAb ELISA kits were used for the detection of serum levels of oxLDL and IgoxLDL, respectively. Lipid parameters were measured by routine photometric tests. Cox step wise model, Kaplan Meier and log rank test were used for results evaluation and expression.

RESULTS:

The data were divided into tertiles. The first tertile of patients (oxLDL 47.24 U/L) had worse prognosis of survival for 36 months (p=0.066) than the other two (second tertile boundaries 65.6 U/L). The second and third tertile showed no obvious difference between each other, generally said the patients with oxLDL levels higher than 47 U/L had almost the same survival rate. Expectedly, the values of oxidized LDL correlate with LDL-C as well as apo B values correlated with LDL-C and apo A with HDL-C, respectively. OxLDL antibodies showed significant correlation between oxLDL antibody titre and total cholesterol, LDL cholesterol and triglycerides. The probability of survival in patients with high levels of IgoxLDL (more than 549.72 IU/L) was significantly lower (p<0.01).

CONCLUSIONS:

The examination of antibodies against oxLDL as a marker of oxidative stress in serum confirmed their negative effect on the survival in HD patients. Oxidized LDL had positive effect on survival. Conceivable principle is that LDL also serves as a marker of nourishment status, and moreover, higher levels of LDL represent more substrate for oxidation.The study was supported by research project MSM 0021620819.

CHANGES IN MYOCARDIAL DEPOLARIZATION AND REPOLARIZATION PROCESSES ASSOCIATED WITH HAEMODIALYSIS ARE RELATED TO CHANGES IN THE RA SYSTEM: A SELECTIVE ALDOSTERONE BLOCKER CAN BE EFFECTIVE FOR THE PREVENTION OF VENTRICULAR ARRHYTHMIA

Abstract

INTRODUCTION AND AIMS:

In patients undergoing maintenance dialysis, arrhythmias frequently develop in association with haemodialysis (HD) procedures, suggesting the influence of fluid removal and the changes in electrolytes and neurohumoral factors on myocardial action potentials. We have reported on changes in signal-averaged electrocardiogram (SAE) (JJSDT 36:1685,2003) and increases in QT dispersion (difference between the maximum and minimum QT intervals:QT-d) (JJN 50:481,2008) during the procedures of HD.Changes in SAE indicate heterogeneity of the myocardial depolarization process, while the increases in QT-d, heterogeneity of the repolarization process.The root mean square voltage in the terminal 40 ms of the QRS (RMS40), an indicator for SAE, and QT-d were determined in the same patients before and after HD and the changes (δ) in these parameters were measured for their correlations with fluid removal rate, findings from holter electrocardiograms (ECG) and changes in the laboratory data including neurohumoral factors and RA system.

METHODS:

The subjects were 121 patients under 80 years of age and in stable conditions after excluding those with cardiomyopathy, myocardial infarction, chronic atrial fibrillation or conduction disturbance. Their primary diseases were diabetic nephropathy (49 patients), chronic glomerulonephritis (26) and others (46). Fluid removal rate during HD was 2.5±2.2%.Before and after HD, RMS40 was determined by using a multifunction electrocardiograph and QTc-d was measured using an instrumentation software and corrected by the heart rate.

RESULTS:

1.RMS40 (1)Changes: increase from 53±27 to 57±32 μV (p<0.05). (2)Relationships with δRMS40: positive correlations with δplasma renin activity (p<0.0001), δangiotensin I (p<0.05) and δaldosterone (p<0.01). (3)Relationship with holter ECG: no late potentials in any patients in grade 0 (Lown's classification) group.2.QTc-d (1)Changes: increase from 60±23 to 74±26 ms (p<0.001). (2)Relationship with δQTc-d: inverse correlation with δaldosterone (p<0.05). (3)Relationship with holter ECG: no significant changes in grade 0 group but significant increases in groups 1 to 4 (p<0.001).3.Relationships of δRMS40 and δQTc-d with fluid removal rate or changes in other data: no correlations were found.

CONCLUSIONS:

1.The changes in SAE and the increases in QT-d indicated that HD was involved in the inducibility of ventricular arrhythmias. The determination of these parameters was useful.2.These changes were related to those in the RA system.3.The control of the RA system, in particular that of aldosterone is important for the prevention of ventricular arrhythmias associated with HD. The use of a selective aldosterone blocker is considered to be useful for oliguric or anuric patients on maintenance dialysis who are not expected to develop hyperkalemia.

CARDIAC TROPONIN T AS A PROGNOSTIC BIOMARKER IN ESTABLISHED RENAL FAILURE

Abstract

INTRODUCTION AND AIMS:

Troponin (Tn) proteins are the gold standard of biomarkers in myocardial injury/infarction. Both TnT and TnI are sensitive and specific in general, but can be altered in non cardiac conditions such as renal failure, sepsis and acute stroke. Cardiovascular disease, left ventricular hypertrophy, inflammation, sepsis, abnormal protein metabolism and clearance are common in end stage renal disease. Many hypotheses have been put forward for the elevation of Tn, in the absence of myocardial disease in dialysis patients. How do we interpret raised Tn and does it have a diagnostic or prognostic value? This study measured TnT in our haemodialysis population and audited outcome (mortality) over 36 months.

METHODS:

We studied an unselected haemodialysis population. None had cardiac symptoms at time of analysis. Analyses were performed on predialysis monthly bloods for TnT, TnI, CRP, PTH, and cholesterol. All case records were reviewed for ECG's and echocardiograms. Outcome and mortality data were recorded and cohorts were followed up for 36 months. Statistical analyses were performed using SPSS computer software.

RESULTS:

The study started with 141 patients, mean age 60, mean duration of dialysis 39 months. ECG's were reviewed in 89% of patients and 74% had echocardiograms. Ischaemic heart disease was diagnosed in 41 patients (29%) and diabetes in 29 (20.5%). TnT was raised (>0.03) in 63 patients (45%) and TnI was elevated (>0.2) in 5 of 135 patients (3.7%). TnT, TnI, CRP and PTH were all skewed in distribution and results are represented as median and (interquartile range). TnT = 0.028 (0.07), TnI = 0.019 (0.04), CRP = 12 (28), PTH = 26 (30), cholesterol = 3.53 (0.92). Logistic regression analysis showed that TnT was a very significant factor (OR: 1.25, p<0.001) and that low cholesterol was significant (OR: -0.387, p<0.071) in relation to outcome (death). Diabetes, history of ischaemic heart disease, ECG and echocardiography findings and duration of dialysis had no significant association with outcome.Actuarial survival curves over 36 months showed a significant difference in outcome between patients with normal and raised TnT values (Cox log rank p<0.005). Mortality rates at 12, 24 and 36 months were 19%, 32% and 34% respectively in the normal TnT group. Mortality data at 12, 24 and 36 months were 42%, 63% and 73% in the raised TnT group.

CONCLUSIONS:

TnT was marginally elevated in almost half of the haemodialysis patients whereas TnI was normal. Patients with elevated TnT had a significant poorer survival and this was independent of age, diabetes, history of heart disease, ECG and echocardiography results. The elevated TnT levels may represent sub-clinical myocardial injury. Elevated TnT appears to be a strong negative prognostic factor for patients on haemodialysis and perhaps TnT should be used as a routine biomarker to assess those patients most at risk.

EFFECT OF SINGLE SESSION OF HAEMODIALYSIS ON ARTERIAL STIFFNESS

Abstract

INTRODUCTION AND AIMS:

Large arteries in ESRD patients are characterized by dilatation, wall thickening, and high frequency of calcified atherosclerotic plaques leading to hemodynamic changes such as increased arterial stiffness, pulse wave velocity (PWV), and a marked effect of arterial wave reflections on central arteries. The tonometery of peripheral arteries can reliably be used to measure aortic stiffness by calculating Aortic PWV. Many studied proved that increased aortic stiffness is a predictor of mortality in ESRD patients undergoing haemodialysis (HD). There are conflicting reports on effect of interdialytic weight gain on PWV. The current study was undertaken to analyse the effect of single session of haemodialysis on arterial stiffness measured by PWV.

METHODS:

This prospective study was started at Nephrology department of Royal Melbourne hospital in September 2007. Total eleven patients were enrolled. Multiple hemodialysis session were monitored on each patient. Assessment of arterial wave form, PWV, was performed noninvasively with the commercially available SphygmoCor system (AtCor Medical). Peripheral pressure wave forms were recorded from the radial artery (non fistula arm) at the wrist, carotid and femoral arteries. The average of three measurements was used. This method has high reproducibility rate.

RESULTS:

There was statistically significant increase in PWV 2hrs after start of HD from 7.19 to 8.49 (p=0.014). The decrease in PWV was recorded from 2hrs to post HD. There was no statistically significant difference in PWV from 2hrs to post HD and pre HD to post HD. As the difference in PWV at 2 hrs was significant, the change in PWV from pre HD to 2hrs was considered only for further analysis. The association between changes in PWV was checked with all demographic and hemodynamic parameters among which SBP (p≤0.001), DBP (p≤0.001), MAP (p≤0.001), age (p =0.018), BF (p≤0.001), albumin (p=0.005), calcium (p=0.003) and phosphorus (p=0.003) were found significant. The multivariate stepwise regression analysis showed that 64.9% of total variation in PWV was explained by the change in MAP (ß=0.043, p<0.001), BF (ß=0.004, p<0.001) and phosphorus (ß= -0.387, p=0.014).The increase in MAP and BF were causing increase in PWV while phosphorus was having negative impact.

CONCLUSIONS:

Overall single hemodialysis session has no effect on arterial stiffness, however during first 2 hours arterial stiffness increases which comes to near base line at the end of dialysis.

FLUID OVERLOAD AND MALNUTRITION MONITORING USING BIOIMPEDANCE SPECTROSCOPY (BIA) IN DIFFERENT STAGE OF CHRONIC KIDNEY DISEASE (CKD)

Abstract

INTRODUCTION AND AIMS:

The increased mortality risk in HD patients as a consequency of malnutrition and fluid disturbances are well established.Additionally it was shown (Wizemann et al NDT plus 2008) that fluid overload >2.5 L leads to a significantly increased mortality risk. Bioimpedance spectroscopy combined with a body composition model enables the determination of fluid overload (FO) and nutrition status (Wabel et al., NDT 2008) useful in the assessment of prevalence and risk in different stage of CKD patients.

METHODS:

Bioimpedance water compartments and nutrition parameters including: total body water (TBW; L), extracellular water (ECW; L), intracellular water (ICW; L), Lean Tissue Mass (LTM; kg), Fat mass (FM; %), Adipose Tissue Mass (ATM; kg and %) and the level of overhydration (OH;L and %) were measured, in 100 CKD patients divided into 2 equal groups (N=50) with eGFR more or less than 30 ml/min/m² b.w. using a BCM-Body Composition monitor which has been validated previously (Fresenius Medical Care, Germany).

RESULTS:

The BIA results are presented in table as below. The significant increase of OH has been observed in the group with eGFR < 30 ml/min/m² vs. group with GFR ≥ 30 ml/min/m² (3,72±2,73 L vs. 1,81±2,38 L). The BIA nutrition parameters were not different between each of invastigated groups.

CONCLUSIONS:

The BCM allows fluids overload (FO) to be monitored easily and could be invaluable in the correction of excess FO in patients with progressive CKD. Incorrect treatment of excessive fluid overload significantly increases mortality risk in patients with stage 4-5 of CKD.

ARTERIAL STIFFNESS AND COGNITIVE FUNCTION IN DIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Increased arterial stiffness in dialysis patients (pts) is recognized as an established cardiovascular (CV) risk factor. Moreover, the majority of these pts present with impaired cognitive function (CF) with only 13% of them having normal findings. Recently, markers of arterial stiffness such as pulse wave velocity (PWV) and pulse pressure were found to be associated with cognitive decline in the aging population.The aim of our study was to assess arterial stiffness and CF in hemodialysis (HD) and peritoneal dialysis (PD) pts and investigate whether there was a possible correlation between the above parameters as well as with other CV risk factors.

METHODS:

In this pilot, cross-sectional study 49 steady pts were included, 26 on HD and 23 on PD. Pts with previous stroke and depression were excluded. There were 32 (65%) men (mean age 61±15 ys with similar mean age for both modalities). Arterial stiffness was evaluated by measurement of PWV between carotid-femoral arteries (PWVC-F) before the middle week HD session and during a regular visit for the PD pts.On the same time we assessed CF by using 4 questioners standardized for the country general population [Geriatric Depression Scale (GDS),Abbreviated Mental Test Score (AMTS),Clock Test and Instrumental Activity of Daily Living (IADL)].Thirty two (65%) out of the overall pts were hypertensives (HTs) receiving treatment (43% ACEi/ARB, 43% CCB),14 (29%) had diabetes mellitus (DM),10 (20%) had established CV disease (CVD),20 (41%) pts were receiving statins,35 (71%) vit D analogs and 7 (14%) were smokers. Mean systolic,diastolic and pulse BP was 133±21, 78±11 and 55±20 mmHg respectively (without significant difference between HD and PD pts), while mean Kt/V was 1.3±0.22 and 2.3±0.7 in HD and PD pts respectively.

RESULTS:

There was no difference between men and women regarding PWVC-F and CF scores. Interestingly, pts with dementia according to Clock test score had significant worse PWVC-F compared with pts with cognitive impairment (p=0.026). There was no difference between HD and PD modality regarding PWVC-F, however PD pts revealed significant better Clock test than HD pts (1/4 had dementia and 3/4 had cognitive impairment while in HD pts it was the opposite,p<0.001). Comparing CVD and non-CVD pts as well as DM and non-DM pts there was no difference regarding PWVC-F. However, CVD pts had worse CF (IADL score 20±8.17 vs 13.4±6.51, p=0.009) and all diabetics had mild dementia. HTs had similar PWVC-F levels and CF scores compared with non-HTs. However, pts receiving CCB and vit D analogs had significantly better CF (Clock test p=0.003,p=0.03), while treatment with ACEi/ARB and statins did not affect PWV and CF. Smokers had cognitive dysfunction (IADL p<0.001, Clock test p=0.001).

CONCLUSIONS:

CVD, DM and smoking could possibly have negative impact, while treatment with CCB and vit D analogs a positive one on CF in dialysis pts. PD pts revealed less CF decline compared with HD pts. Pts with worse Clock test had significantly increased PWV, implying that arterial stiffness and CF could be associated in dialysis pts.

LOWERING DIALYSATE CALCIUM CONCENTRATION FROM 3.0 mEq/L TO 2.5 mEq/L ATTENUATES THE PROGRESSION OF ABDOMINAL AORTIC CALCIFICATION IN PATIENTS ON CHRONIC HAEMODIALYSIS

Abstract

INTRODUCTION AND AIMS:

Vascular calcification is an independent determinant of cardiovascular events in patients on chronic haemodialysis (HD). “The Kidney Disease Outcome Quality Initiative Guideline” recently recommended, as “OPINION”, that the dialysate calcium concentration be 2.5 mEq/L to prevent the metastatic calcification. However, the relation between dialysate calcium concentration and vascular calcification has not been clarified. This study was planned to clarify the effect of lowering dialysate calcium concentration from 3.0 mEq/L to 2.5 mEq/L on the progression of abdominal aortic calcification in HD patients.

METHODS:

We enrolled 11 HD patients (lowering group), whose dialysate calcium concentration was switched from 3.0 mEq/L to 2.5 mEq/L during three years. As a control group, another 11 HD patients (matched in age, sex and basal renal disease), whose dialysate calcium concentration was maintained as 3.0 mEq/L, were selected. These 22 patients received HD at least for 6 years and underwent abdominal computed tomography (CT) three times at an interval of approximately three years. The aortic calcification index (ACI) was quantified morphometrically using abdominal CT films (range of ACI, 0–240). The progression rate of aortic calcification was calculated as ΔACI/year.

RESULTS:

The values of the first ACI and ΔACI/year, until 3 years before, were not different between lowering and control groups (first ACI, 37.2 ± 42.6 vs 49.7 ± 37.6; first ΔACI/year, 7.2 ± 6.0 vs 4.8 ± 4.6). In lowering group, the second ΔACI/year, 3 years later that was switched dialysate calcium concentration from 3.0 mEq/L to 2.5 mEq/L, was significantly decreased compared with the first ΔACI/year (7.2 ± 6.0 vs 4.7 ± 5.3, p < 0.0415, Wilcoxon signed rank test). On the other hand, in control group the second ΔACI/year was significantly increased compared with the first ΔACI/year (4.8 ± 4.6 vs 9.3 ± 7.2, p < 0.0099, Wilcoxon signed rank test).

CONCLUSIONS:

Lowering dialysate calcium concentration from 3.0 mEq/L to 2.5 mEq/L attenuats the progression of abdominal aortic calcification in patients on chronic haemodialysis.

PROINFLAMMATORY CYTOKINES, ADHESION MOLECULES AND ATHEROSCLEROSIS IN CHRONIC HAEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Uraemia is considered a chronic inflammatory state associated with increased incidence of atherosclerotic cardiovascular disease (CVD) which is the leading cause of mortality for end-stage renal disease patients. The aim of the present study was to investigate the probable association between markers of inflammation and endothelial cell adhesion molecules with the extent and severity of atherosclerosis in chronic haemodialysis (HD) patients.

METHODS:

Seventy-two haemodialysis patients (37 men, mean age 58,7± 14,8 years, mean HD duration 83 ±77,9 months) were included. Eleven (15,3%) patients had diabetes and 30 (41,7%) had a history of CVD. Atheosclerosis was assessed by measuring intima-media thickness (IMT) and plaque score (PS) of the carotid arteries with an ultrasound scanner. Serum CRP was measured by nephelomerty and serum levels of proinflammatiory cytokines IL-6 and TNF-α and adhesion molecules ICAM-1 and VCAM-1 by ELISA.

RESULTS:

In bivariate regression analysis IMT was significantly correlated with age (r= 0,583 p<0,000) and serum CRP (r=0,292 p=0,013), TNF-α (r=0,234 p=0,048), ICAM-1 (r=0,289 p=0,014) and VCAM-1 levels (r=0,318 p=0,007). Multivariate stepwise regression analysis (Adj.R² = 0,470 p = 0,000) showed that age (s.beta=0,498 p<0,000), systolic blood pressure (s.beta=0,236 p=0,010), ICAM-1 (s.beta=0,273 p=0,004) and VCAM-1 levels (s.beta=0,207 p=0,026) were independent predictors of IMT values of cIMT. Carotid PS correlated significantly to age (r=0,591 p<0,000), serum CRP (r=0,326 p<0,005), IL-6 (r=0,319 p=0,010), TNF-α (r=0,241 p<0,042) and VCAM-1 levels (r=0.235 p<0,047). Age (s.beta=0,401 p<0,001), CRP (s.beta=0,251 p=0,023) and IL-6 (s.beta=0,230 p=0,026) levels remained significantly correlated to PS in the multivariate analysis (Adj.R²= 0,368 p = 0,000). No significant correlations were observed between IMT or PS with other risk factors for atherosclerosis including sex, smoking, diabetes, history of CVD, serum lipids, haemoglobin, albumin, calcium, phosphorus and iPTH.

CONCLUSIONS:

In chronic haemodialysis patients, elevated serum ICAM-1 and VCAM-1 levels are associated with increased carotid IMT, a marker of early atherosclerosis whereas increased CRP and IL-6 levels are associated with more advanced atherosclerotic lesions. These results support the concept that endothelial adhesion molecules play a role mainly in the initiation of the atherosclerotic process which is progressed and propagated by a chronic inflammatory response.

SCREENING, DIAGNOSIS AND INTERVENTION OF ASYMPTOMATIC CORONARY ARTERY DISEASE AT THE TIME TO START RENAL REPLACEMENT THERAHY IS ASSOCIATED WITH REMARKABLE BETTER LIFE EXPECTANCY IN DIABETIC NEPHROPATHY PATIENTS ON DIALYSIS

Abstract

INTRODUCTION AND AIMS:

The numbers of patients who have diabetic nephropathy (DN) and end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) are increasing worldwide. Their mortality is still high compared with non-diabetic patients, however no specific therapeutic strategies have been found to improve mortality in these patients in previous studies. We have continued to perform early evaluation of asymptomatic coronary artery disease (CAD) using cardiac biomarkers besides electrocardiogram and ultrasound echocardiogram. The aim of the present study is to determine whether our attempt is effective to improve prognosis in DN patients on RRT.

METHODS:

We retrospectively analyzed the mortality in all consecutive patients (N=443) who have started RRT at our blood purify center since September 2000 to December 2008. Demographic, clinical and laboratory variables at the initiation of RRT, including comorbidity, time on nephrological care before RRT, duration of erythropoietin (EPO) treatment prior to RRT, and referral to cardiologists according to asymptomatic CAD screening, were analyzed to identify the factors favorable for survival by multivariate Cox regression analysis. Analysis was conducted at the end of December 2008.

RESULTS:

Seventeen patients were excluded (transplantation 6, lost to follow 11). Patients were divided into three groups due to the causes of ESRD; CGN group (chronic glomerulonephritis; N=116), DN group (N=162) and OTHER group (other causes; N=148). Average observation period was 30.2 months. Total death was 152 including 32 patients who died within 3 months of starting RRT. Coronary angiography was performed in 20%, 46% and 11% of asymptomatic patients with CGN, DN and OTHER groups, respectively (p<0.001). 5-year survival rate in DN group was extremely high at 69.9% compared with CGN (60.0%) and OTHER (29.6%) groups (p<0.001). Factor independently correlated with better survival were asymptomatic CAD screening at the time of RRT start (HR 0.652, 95%CI 0.439-0.968) and the duration of EPO use (HR 0.967, 95%CI 0.941-0.994), whereas age, history of cerebrovascular disease and high level of serum calcium were independently associated with poor outcome.

CONCLUSIONS:

Early screening, diagnosis and intervention of asymptomatic CAD patients at the time to start RRT is promising strategy for improving survival in DN patients on RRT.

A COMPARATIVE STUDY OF THE EFFECTS ON PULSE WAVE VELOCITY (PWV) IN HEMODIALYSIS (HD) PATIENTS TREATED BY SEVELAMER WITH LOW DOSE CALCIUM CARBONATE OR CALCIUM CARBONATE ALONE.THREE-YEARS FOLLOW-UP

Abstract

INTRODUCTION AND AIMS:

Cardiovascular disease is a major cause of morbidity in patients with end-stage renal failure. Increasing evidence suggests that prolonged use of calcium carbonate increases the total body calcium load, and potentially increases the risk of cardiovascular and soft tissue calcification.Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium-free, and metal-free. It may also attenuate coronary and aortic calcification and has a number of other beneficial effects on lipid metabolism. On the other hand, arterial stiffness measured by pulse wave velocity (PWV) is an independent risk factor for morbidity in end stage renal failure patients, and treatment with sevelamer was reported to attenuate the progressive increase in PWV in HD patients.The present study was performed to assess the effect of sevelamer administration on PWV in HD patients treated with calcium carbonate.

METHODS:

We performed a randomized prospective clinical trial to compare the effect of calcium carbonate alone and sevelamer with low dose calcium carbonate on PWV.A total of 35 HD patients, who had been treated with calcium carbonate as a phosphate binder, were enrolled into the study. The patients were randomly divided into the sevelamer with low dose calcium carbonate group (group A) and calcium carbonate alone group (group B). PWV was measured every 6 months for 3-years study period. Serum biochemistry parameters were also assessed. Data are expressed as means ± SD, and comparison between groups was evaluated by student's t-tests.

RESULTS:

In group A, the dose of calcium carbonate could be reduced significantly from 3.2±1.9g/day to 1.0±0.8g/day with serum phosphate values maintained below 6 mg/dL by the addition of 2.6±0.6 g/day sevelamer. In group B, the dose of calcium carbonate needed to be administered from 2.4±0.7g/day to 1.7±0.8 g/day. In both group, there was not significant change in PWV from 2059 ± 555 to 2021± 533 cm/sec (P=0.76, Group A) and from 2094±69.3cm/sec to 1971±741 cm/sec (P=0.44, Group B). In both group serum calcium, phosphate and calcium x phosphate product remained unchanged. Only in group A, low density lipoprotein down from 84.7±24.7mg/dL to 65.1±20.6 mg/dL (P<0.05).

CONCLUSIONS:

The level of low density lipoprotein was significantly decreased after the adinistration of Sevelamaer. The dosage of calcium carbonate was successfully reduced by adding sevelamer to maintain serum phosphate levels below 6 mg/dL. However, PWV was not significantly improved.

THE EFFECT OF STATIN ON THE KINETICS OF ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORT AND C-REACTIVE PROTEIN IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS:

Although the markedly increased risk of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) is well established, the role of uremic dyslipidemia relative to other novel CVD risk factors remains uncertain. Dyslipidemia may be a major contributor in this process and can be influenced by statins. Statins may exhibit additional inhibitory effects on the atherogenesis by a reduction of the inflammatory marker C-reactive protein (CRP). Erythrocyte sodium-lithium countertransport (Na/LiCT) is a sensitive membrane protein and has been reported to be abnormal (low Km) in hemodialysis patients. The activity of Na/LiCT has a positive correlation with the level of CRP in high cardiovascular risk patients. There is evidence suggesting that simvastatin can reduce the level of CRP and the other acute phase reactants in hemodialysis patients. We have hypothesized that simvastatin may decrease the CRP level and would improve the kinetics of Na/LiCT.

METHODS:

Twenty hemodialysed patients were divided into 2 groups. The study group 1 (n=10) has received simvastatin 10 mg daily for 4 months and the placebo group (n=10) has received placebo tablets for the same period as in the study group. We have measured serum CRP level, ESR, lipid profiles and the kinetics of Na/LiCT in all 20 patients before and after taking simvastatin.

RESULTS:

After 4 months, the CRP level was decreased in the study group more than in the placebo group (18.6% reduction in the study group vs 1.0% reduction in the placebo group). Before the treatment period, the Km for external sodium of erythrocyte of Na/LiCT was lower than that of normal controls in both groups of patients (56±3 vs 76±2 in group 1, P<0.01 and 50±2 vs 76±2 in group 2, P<0.01). After 4 months of simvastatin, the Km for external sodium was significantly improved (56±3 vs 69±5, P<0.01).

CONCLUSIONS:

These results show those simvastatin exhibit comparable favorable effects on lipid profiles and the reduction of CRP level in hemodialysis patients. Moreover, the improvement of the kinetics of erythrocyte Na/LiCT as shown in this ESRD population, may indicate that these statins exhibit favorable effects on oxidative stress.

RISK FACTORS OF PERIPHERAL ARTERIAL DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

INTRODUCTION AND AIMS:

Peripheral arterial disease (PAD) is a predictable marker of hypertension, coronary heart disease, cerebrovascular disease and its prevalence among chronic kidney disease (CKD) patients is apparently increasing. Ankle-Brachial Index (ABI) is regarded as an easy, reliable, and noninvasive measure of the presence and severity of lower-extremity PAD (ABI<0.9). The aims of this study are to elucidate the prevalence of PAD affecting lower limbs using ABI, and to assess the risk factors of PAD in patients with CKD.

METHODS:

ABI was measured by automatic volume-plethysmographic device, VP 2000 PWV(Colin Medical Technology, Komaki, Japan). One hundred forty five CKD patients who were performed ABI examination were categorized into CKD stage I to V and the prevalence of PAD in each stages was analyzed. We also reviewed the clinical characteristics and evaluate the risk factors of PAD, retrospectively.

RESULTS:

Of one hundred forty five CKD patients, 69 patients were on chronic dialysis therapy.Thirty six patients of 145 CKD patients (24.7%) showed PAD (ABI<0.9). The incidence of PAD increased significantly according to the stages of CKD (P=0.037). Hyperlipidemia, coronary artery disease and cerebrovascular disease in patients with CKD and PAD were significantly more prevalent compared to CKD patients without PAD (ABI≥0.9) (P=0.013, P=0.000, P=0.024, respectively). The prevalence of hypertension and dyslipidemia in non-dialysis CKD patients with PAD was significantly higher (p=0.017, p=0.005, respectively) than those of patients without PAD and eGFR of patients with PAD was significantly lower than that of patients without PAD (p=0.012). The incidence of cardiovascular disease and serum level of LDL-cholesterol in patients on dialysis with PAD was significantly higher than those of dialysis patients without PAD (p=0.030, p=0.007, respectively).After a multivariate analysis, PAD(ABI <0.9) was not significantly associated with increased age, diabetes mellitus (DM), increased pulse pressure, decreased serum albumin level.

CONCLUSIONS:

With the above results, it is speculated that the incidence of PAD in patients with CKD increases according to the magnitude of renal dysfunction.

AORTIC CALCIFICATION SCORE AND ARTERIAL STIFFNESS IN HEMODIALYSED PATIENTS – CORRELATION AND DETERMINANTS

Abstract

INTRODUCTION AND AIMS:

Vascular calcification and increased arterial stiffness are common, interrelated and associated with increased morbidity and mortality in chronic kidney disease (CKD). Few studies addressed the associations among vascular calcification, aortic stiffness and traditional or non-traditional” cardiovascular risk factors in CKD patients.Aims of the study were to evaluate the relationships among aortic calcification score and aortic stiffness, as well as their association with traditional and non-traditional” risk factors in a cohort of non-diabetic long vintage hemodialysis (HD) patients.

METHODS:

Retrospective single centre study on 155 adult non-diabetic HD patients. Aortic calcification score was assessed on a lateral plain radiograph of the abdomen according to Kaupilla, aortic button calcifications on a thorax radiograph and echography was used to evaluate valvular calcifications and carotides plaques. Arterial stiffness was measured by pulse wave velocity (PWV) with a SphygmoCor device. Data on traditional” cardiovascular risk factors (age, gender, smoking, high blood pressure and blood lipids), inflammation and calcium phosphate metabolism were electronically retrieved from patients file. Time-averaged (24 months) values were used.

RESULTS:

Patients (56% male, 45% glomerulonephritis, median hemodialysis vintage 9 years) had a median age 55 years (range 18-79). Median aortic calcification score was 5 [i.q.r 0-12]; in 31% patients the score was 0. The prevalences of carotids plaques, aortic button and valvular calcifications were 69%, 59% and 49%, respectively. Mean PWV was 7.7±2.3m/s. Aortic calcification score and pulse wave velocity were significantly correlated (r2=0.16; p<0.001). In multivariable regression analysis, increasing age and macro inflammation (serum C-reactive protein>10mg/L) were associated with a higher aortic calcification scores, while age and parameters of mineral metabolism (increased time-averaged serum calcium, phosphate and calcium phosphate product) were related to higher PWV. Excepting age, “traditional” risk factors had little influence on both aortic calcification score and PWV.

CONCLUSIONS:

Aortic calcification score and PWV are simple and useful in-office methods to evaluate the extent of vascular calcifications in HD patients, both anatomically and functionally. The aortic calcification score appears to be more linked to inflammation and atherosclerosis, in opposition to pulse wave velocity which, also closely correlated to the calcification score, seems to be more linked to calcium-phosphate abnormalities and arteriosclerosis. Excepting age, “traditional” cardiovascular risk factors seems to play a minor role in defining aortic calcification score or PWV in this long HD vintage, non-diabetic cohort.

ACUTE EFFECT OF HEMODIALYSIS ON PULSE WAVE VELOCITY AND AORTIC PRESSURE AUGMENTATION

Abstract

INTRODUCTION AND AIMS:

Increased aortic stiffness markers have emerged as powerful predictors of survival in hemodialysis patients. The aim of our study was to demonstrate whether the hemodialysis procedure per se can cause a change in pulse wave velocity (PWV) and aortic pressure augmentation (AIx) in well dialyzed patients.

METHODS:

We studied ten patients (8 males, 2 females) on chronic hemodialysis. The mean age was 47±16 years and the duration of hemodialysis was 8 months for two patients and between 7 and 33 years for the rest of them. They were receiving hemodialysis three times a week and each session lasted 4 to 5.5 hours. Patients were studied before and immediately after a hemodialysis session. Pulse contours were obtained noninvasively by applanation tonometry using SphygmoCor^TM device. From radial arterial waveform an aortic waveform was derived in real time with a specially designed software (SphygmoCor^TM; PWV Inc., Westmead, Sydney, Australia) and the AIx was calculated as the difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height. The common carotid artery and the femoral artery were used to determine PWV.

RESULTS:

Volume reduction with hemodialysis resulted in a decrease of body weight from 70±11 kg to 67.6±10.4 kg (P<0.002). Comparison of changes in hemodynamic parameters as well as in PWV and AIx from baseline and after dialysis presents.

At a baseline, PWV was normal in 8 out of 10 patients, and reached 12 m/s only in 55-year and 80-year old patient. With dialysis, PWV increased significantly above 11 m/s in additional 5 patients. In the rest of 4 patients PWV did not change. Hemodialysis procedure tended to increase the average AIx. The hemodialysis induced increase in PWV was independent of the ultrafiltration volume or the change in blood pressure as shown in table 2.

CONCLUSIONS:

We noticed a direct effect of a hemodialysis session on PWV and AIx. The direction of changes in AIx and PWV recorded following dialysis was the same. A higher AIx in a group of increased PWV after hemodialysis could be a marker of abnormal arterial structure, suggesting that pulse wave analysis may be used to detect a subset of high-risk hemodialysis patients.