Risk factors for progression of aortic arch calcification in patients on maintenance hemodialysis and peritoneal dialysis

Vascular calcification is accelerated during dialysis and is known to be an important risk factor for cardiovascular disease. Progression of aortic arch calcification (AoAC) can be simply estimated with an AoAC score (AoACS) using plain chest radiography. The objective of this study was to evaluate risk factors for AoAC progression. The enrolled subjects were 125 newly treated hemodialysis patients and 59 peritoneal dialysis patients. In the patients who had undergone chest radiography before initial dialysis therapy and every year, we estimated AoACS and then divided the patients into two groups based on the presence or absence of AoAC progression. We also compared the baseline clinical and biochemical profiles in the two groups. Eighty‐five (46.2%) were men (mean age, 58.6 ± 12.7 years). Seventy‐six patients (41.3%) had AoAC before initial dialysis, with a mean AoACS of 13.0 ± 20.4%. The mean duration of follow‐up was 2.7 ± 1.0 years. Half of the patients (50%) had progressive AoAC. Age >65 years (p = 0.003), dialysis duration (p = 0.004), diabetes (p = 0.015), and the presence of AoAC at baseline (p = 0.001) were related to AoAC progression. No significant association was found between AoAC progression and the baseline clinical parameters, including gender, obesity, hypertension, and dialysis modality. In a multivariate analysis, dialysis duration (p = 0.003) and the presence of AoAC at baseline (p < 0.001) were independent risk factors for AoAC progression in patients undergoing dialysis. The duration of dialysis and the presence of AoAC before initial dialysis were significantly related to the progression of AoAC in these patients. The results suggest that patients should be carefully managed from the predialysis stage to prevent AoAC progression and to reduce cardiovascular morbidity.     

Left ventricular mass index and aortic arch calcification score are independent mortality predictors of maintenance hemodialysis patients

To analyze predictive factors for all‐cause mortality, cardiovascular (CV) mortality, nonfatal CV events (CVE) in maintenance hemodialysis (MHD) patients, and to compare the effects of standard hemodialysis (HD) and online hemodiafiltration (HDF) on these factors and outcomes. A total of 333 MHD patients were prospectively followed up for 50 ± 15 months and all‐cause death, CV death and CVE were registered. At the baseline, demographic, clinical, and laboratory data of the whole population were recorded. Then, patients were stratified into two groups according to the dialysis modalities, HD (n = 268) and HDF (n = 65). At the end of 6th month, clinical and laboratory data were recorded again. The predictive factors at baseline for all‐cause mortality, CV mortality, and CVE were analyzed by Cox regression. The effects of HD and HDF on these factors at the 6th month and long‐term outcomes were compared by t‐test and Kaplan–Meier method, respectively. Age, gender, left ventricular mass index (LVMI), aortic arch calcification score (AoACS), hemoglobin (Hb) <10 g/dL, and ferritin >500 ng/mL maintained independent associations with all‐cause mortality. C‐reactive protein (CRP), LVMI, AoACS, and Hb <10 g/dL were associated with CV mortality. Prior cardiovascular disease (CVD), AoACS and LVMI were independent predictors of nonfatal CVE. Higher body mass index (BMI), body weight, total serum cholesterol, Hb concentration, and lower CRP level, LVMI, and AoACS were found in patients on HDF at the end of the 6th month. Improved outcomes with longer survival time for all‐cause mortality, CV mortality, and CVE were found in HDF group. Age, gender, LVMI, AoACS, Hb, and ferritin were predictors of all‐cause mortality in MHD patients. CRP, LVMI, AoACS, and Hb were associated with CV mortality. Prior CVD, AoACS, and LVMI were independent predictors of nonfatal CVE. HDF could improve BMI, body weight, total serum cholesterol, Hb, CRP, LVMI, AoACS, and long‐term outcomes, including all‐cause mortality, CV mortality, and CVE.     

Coronary and aortic calcifications in patients new to dialysis

Background: Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end‐stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis. Methods: A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification. Results: Forty‐three percent of subjects had no significant coronary artery calcification (total score ≤ 30) and 27% had no detectable aortic calcification. Thirty‐four percent had coronary artery scores that placed them above the 90th percentile for age and sex. Coronary artery calcification was significantly associated with a history of coronary artery disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p = 0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were independently associated with the extent of coronary artery calcification. Age (p < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the extent of aortic calcification. Conclusions: A large fraction of patients new to hemodialysis had no evidence of coronary artery or aortic calcification. Coupled with the extensive vascular calcification reported by others in prevalent dialysis patients these findings suggest that dialysis‐specific factors contribute to calcific vascular disease in ESRD.     

Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis

The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all‐cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron‐beam computed tomography. Fifty‐six patients underwent a second electron‐beam computed tomography after a 15‐month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross‐sectional study, HD vintage and high‐sensitive C‐reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan‐Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all‐cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15‐month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all‐cause deaths.     

Anatomical factors associated with left innominate vein stenosis in hemodialysis patients

Central venous stenosis remains a challenge in hemodialysis patients. Venograms have shown that left innominate vein (LIV) stenosis often occurs in front of the trachea, where it crosses the aortic arch, suggesting that there may be an anatomical factor involved, such as iliac vein compression syndrome. The goal of this study was to determine whether LIV stenosis can be attributed to compression. From September 2008 to December 2011, 19 hemodialysis patients (ten women, nine men) with symptomatic venous hypertension of the upper‐left extremity were enrolled in this study. Venography and multidetector computed tomography were used to determine the location of the venous stenosis and to assess LIV anatomy. LIV diameter and the space between the sternum and aortic arch were compared between the LIV stenosis (LIVS) group (n = 9) and the non‐LIV‐stenosis (NLIVS) group (n = 10). The mean age of the cohort was 63 ± 17.3 years. The mean LIV diameter was 1.69 ± 1.55 mm in the LIVS group and 8.71 ± 2.33 mm in the NLIVS group. The space between the aortic arch and sternum was smaller in the LIVS group (4.55 ± 2.67 mm) than in the NLIVS group (15.25 ± 6.12 mm, P < 0.001). A contributing factor to LIV stenosis may be due to anatomical compression of the aortic arch behind the sternum. Preoperative noncontrast computed tomography is recommended for hemodialysis patients to exclude extrinsic compression.     

Intracranial arterial calcification is highly prevalent in hemodialysis patients but does not associate with acute ischemic stroke

Intracranial arterial calcification (IAC) is associated with ischemic stroke in the general population but this relationship has not been examined in hemodialysis patients. We examined the factors associated with IAC and its relationship with acute ischemic stroke in this population. We retrospectively studied 490 head computed tomographic scans from 2225 hemodialysis patients presenting with neurological symptoms at our center (October 2005-May 2009). Intracranial arterial calcification was graded using a validated scoring system. Multivariate regression was used to examine the factors associated with the presence of IAC, its severity, and its ability to predict acute ischemic stroke. Weibull's survival models analyzed the relationship between IAC severity and survival. Ninety-five percent of patients with ischemic stroke had IAC vs. 83% in the nonstroke group (P=0.02). Intracranial arterial calcification severity increased with age (P<0.001), hemodialysis vintage (P<0.001), serum phosphate (P<0.05), and major comorbidities. In patients with multiple computed tomographic scans during the study period, increased IAC severity at baseline was predictive of acute ischemic stroke (P=0.05) on logistic regression analysis. High-grade and not low-grade IAC was associated with worse survival (P=0.008). Intracranial arterial calcification is highly prevalent in hemodialysis patients, especially in those with acute ischemic stroke. Its severity is prognostically significant and associated with risk factors for vascular calcification and may confer a greater risk of acute ischemic stroke. The mechanisms underlying the high incidence of ischemic stroke in this patient group require further comprehensive study.     

The relationship between neutrophil‐to‐lymphocyte ratio and vascular calcification in end‐stage renal disease patients

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri‐aortic calcification (TAC) in end‐stage renal disease (ESRD) patients. Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross‐sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram‐gated 64‐multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.     

Effect of sevelamer on aortic pulse wave velocity in patients on hemodialysis: a prospective observational study

Aortic stiffening and aortic calcification are risk factors for cardiovascular events in hemodialysis (HD) patients, and these 2 risk factors are interrelated. Sevelamer decreases aortic calcification but its effect on aortic stiffness has not been investigated previously. Thirteen HD patients commencing sevelamer treatment and 13 matched controls were followed for 11 months. Aortic pulse wave velocity (PWV), augmentation index (AIx), and levels of inhibitors of vascular calcification (fetuin-A, matrix-GLA-protein, osteoprotegerin/RANKL) were measured at baseline and at the end of follow-up, and the differences between the groups were compared. Determinants of the changes in PWV during follow-up were assessed by multivariate linear regression. At baseline, PWV was 9.93 (2.10) m/s in sevelamer-treated patients and 9.20 (2.84) m/s in control patients (p=0.464). By the end of follow-up, PWV decreased by 0.83 (2.3) m/s in sevelamer-treated patients while it increased by 0.93 (1.88) m/s in controls (p=0.042). The direction of changes in AIx were similar, but not statistically significant. There were no significant differences in the levels of inhibitors of calcification either at baseline or during follow-up. In multivariate linear regression sevelamer treatment, diabetes, heart rate, and C-reactive protein were related to the change in PWV. These data suggest that sevelamer treatment is associated with an improvement in aortic stiffness in HD patients, but it does not seem to affect serum levels of inhibitors of vascular calcification.     

Mini mental status examination (MMSE) in stable chronic renal failure patients on hemodialysis: The effects of hemodialysis on the MMSE score. A prospective study

Cognitive impairment is common in hemodialysis (HD) patients. The mini mental status examination is a simple screening test for dementia. The objectives of this study were to (1) study and compare the predialysis and postdialysis mini mental status examination score and 2 subscores and compare them with those of a control group and (2) determine the factors affecting these scores. This was a prospective study of 54 HD patients, which involved calculation of their predialysis (PrHDSc) and (2–4 weeks later) postdialysis (PoHDSc) scores and comparison of these with the control scores (CoSc). The mean scores for PreHDSc and PoHDSc were 26.5±2.7 and 26.4±3.3, respectively. Both were significantly lower than CoSc, 28.4±1.6 (95% CI for score difference 0.99–2.97, P<0.001). The subscores for orientation, registration, and recall (ORR) and attention (ATT) before and after HD were 14.2±1.3, 14.3±1.8, and 3.5±1.7, 3.2±1.8, respectively. Both were significantly lower than the CoSc, 15.2±1.2 and 4.2±1.1 (P=0.001 and 0.004, respectively). There were no significant differences between the PrHDSc and PoHDSc (P values of 0.87, 0.63, and 0.45, respectively). Patients' PrHDSc correlated positively with PoHDSc and dialysis efficiency measured by the urea reduction ratio and Kt/V (r=0.58, 0.4, and 0.34, respectively). Education level correlated positively with PrHDSc r=0.41 but not PoHDSc. Hemodialysis duration correlated negatively with PrHDSc r=−0.3. There was no correlation among age, chronic renal failure duration, HD frequency, weight loss, systolic or diastolic blood pressure drop, and PrHDSc or PoHDSc. Hemodialysis patients scored significantly less than the control patients. Their score was not affected by HD. This may reflect the stable cognitive function/dysfunction or the mild sensitivity of the test.     

Both pelvic radiography and lateral abdominal radiography correlate well with coronary artery calcification measured by computed tomography in hemodialysis patients: A cross‐sectional study

Introduction Lateral abdominal radiograph is suggested as an alternative to coronary artery computed tomography (CT) in evaluating vascular calcification. Simple scoring systems including pelvic radiograph scoring and abdominal scoring system were utilized to study their correlation with coronary artery calcification. Methods In 106 MHD patients, coronary artery CT, lateral abdominal, and pelvic radiograph were taken. The Agatston scoring system was applied to evaluate the degree of coronary artery calcification which was categorized according to Agatston coronary artery calcification score (CACS) ≥ 30, ≥100, ≥400, and ≥1000. Abdominal aortic calcification was scored by 4‐scored and 24‐scored systems. Pelvic artery calcification was scored by a 4‐scored system. Sensitivities and specificities of abdominal aortic calcification scores and pelvic artery calcification scores to predict different categories of coronary artery calcification were analyzed. We studied the diagnostic capability of abdominal aorta calcification and pelvic artery calcification to predict different CACS categories by calculating likelihood ratios. Receiver operator characteristic curves were used to determine the area under the curve for each of these testing procedures. Findings The prevalence was 48(45.3%), 15 (14.2%), 11 (10.4%), 11 (10.4%), and 11 (10.4%) for CACs > 0, ≥30, ≥100, ≥400, and ≥1000, respectively. The degree of CACs was positively correlated with patient age, prevalence of diabetes, abdominal aorta scores, and pelvic calcification scores. The areas under the curves for different CACS by all X‐ray scoring systems were above 0.70 except pelvic 4‐scored system for diagnosing CACS ≥30, without significant difference (P > 0.05). Discussion Both lateral abdominal and pelvic plain radiographs were demonstrated as acceptable alternatives to CT in evaluating vascular calcification.     

Increased leukocyte aggregates are associated with atherosclerosis in patients with hemodialysis

Little data are available on the role of blood rheology in atherosclerosis in hemodialysis (HD) patients. This study sought to assess the relationship between leukocytes conjugated with platelets (leukocyte aggregates [LA]) and atherosclerosis in patients with HD. The present study included 118 patients on HD. As surrogate markers of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were measured. As an assessment of LA, a method, microchannel array flow analyzer, which makes it possible to directly observe the flow of blood cell elements through the microchannel, was used. We measured a number of LA during 50 μL flow of whole blood through microchannels. In 12 age-matched healthy individuals, a number of LA during 50 μL flow of whole blood was 25.7±5.4, whereas in HD patients it was significantly increased up to 48.2±16.4 (P<0.001). Flow cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates were positively associated with plasma levels of fibrinogen (P<0.01), or serum high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001). In conclusion, we demonstrated hemorheologically that monocyte-platelet conjugates play an important role in aortic stiffness and IMT in HD patients.     

Intima-media thickness of carotid arteries and erectile dysfunction in hemodialysis patients

The prevalence of erectile dysfunction (ED) in hemodialysis (HD) is extremely high. The objective of this study was to evaluate the association between the intima-media thickness of carotid arteries and ED in HD patients. The survey was organized as a cross-sectional study in men aged up to 65 years, in the HD. All respondents voluntarily completed the questionnaire of the International Index of Erectile Function-5, adjusted for the Serbian language, verified routine laboratory analysis, calculated body mass index, demographic structure, duration of dialysis, the presence of hepatotropic viruses and erythropoietin therapy, smoking and drinking alcohol, determined the quality of HD, verified significantly comorbidities and measured the intima-media thickness of carotid artery using the Doppler method. The prevalence of ED in our study was 82.2%. Erectile dysfunction significantly more prevalent in older (P = 0.001) and obese patients (P = 0.047). It is significantly represented in patients with cardiovascular disease (P = 0.006), in those who consume alcohol (P = 0.04) and patients with higher values of intima-media thickness of carotid arteries (P = 0.007). Spearman's coefficient of linear correlation (ρ=-0.34, P=0.006) and linear regression (b=-2.02, P<0.001) indicated a negative association between intima-media thickness and the International Index of Erectile Function score. The prevalence of ED in our patients was 82.2%, more common in older and obese patients, a significant determinant of alcohol consumption and cardiovascular disease. Increased thickness of the intima media of the carotid arteries was associated with a higher incidence of ED.     

Cardiovascular conditions in hemodialysis patients may be worsened by extensive interdialytic weight gain

The risk of death is increased for hemodialysis (HD) patients compared with age-matched healthy subjects, the main reason for this being cardiovascular conditions. This prospective study investigated whether the burden of interdialytic weight gain (IDWG) was of importance for cardiovascular end points and survival. A total of 97 HD patients were studied. The end points included death (reasons given), acute myocardial infarction, or coronary vascular intervention. The extent of ultrafiltration was measured at predefined follow-up points. The IDWG was calculated as ultrafiltration/body weight given in weight%. The burden of IDWG was analyzed. End points occurred in 77 (79%) of the patients during the 5-year study period. The extent of IDWG was higher in those with end points due to cardiovascular reasons (3.77 weight% vs. 3.19 P<0.001), cardiac reasons (P<0.001), congestive heart failure (P<0.01), aortic aneurysm, and intracerebral bleeding (P<0.024). To reduce the risk for cardiovascular events, it is important to avoid too extensive IDWG in HD patients.     

Enhanced expression of hemoglobin scavenger receptor and heme oxygenase‐1 is associated with aortic valve stenosis in patients undergoing hemodialysis

A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase‐1 (HO‐1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non‐HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin‐A (a protein specific to erythrocyte membranes), CD31, CD163, and HO‐1. Morphometric analysis demonstrated that the CD163‐positive macrophage score, the number of CD31‐positive microvessels, and the percentage of glycophorin‐A and HO‐1‐positive area were significantly higher in HD patients than in non‐HD patients (CD163‐positive macrophage score, P < 0.0001; CD31‐positive microvessels, P < 0.0001; glycophorin‐A, P < 0.0001; HO‐1, P < 0.0001). Double immunostaining for CD163 or HO‐1 and macrophages revealed that the majority of CD163‐ or HO‐1‐positive cells were macrophages. Furthermore, CD163‐positive macrophage score was positively correlated with glycophorin‐A, HO‐1‐positive area, and the number of CD31‐positive microvessels (glycophorin‐A, R = 0.66, P < 0.0001; HO‐1, R = 0.50, P < 0.0005; microvessels, R = 0.38, P < 0.01). These findings suggest a positive association among intraleaflet hemorrhage, neovascularization, and enhanced expression of CD163 and HO‐1 as a response to intraleaflet hemorrhage in stenotic aortic valves in AS patients undergoing HD.     

Impact of arterial microcalcification of the vascular access on cardiovascular mortality in hemodialysis patients

Gross vascular calcification seen on imaging studies is common in hemodialysis (HD) patients, and is a significant predictor for cardiovascular mortality in HD patients. We have reported that arterial microcalcification (AMiC) of the vascular access is associated with increased aortic stiffness. This study investigated the impact of vascular access AMiC on cardiovascular mortality in HD patients. The study included 149 HD patients (mean age: 59.1 ± 13.9 years, 86 men and 63 women, 65.8% diabetic) who underwent vascular access surgery. Radial or brachial artery specimens were obtained intraoperatively, and pathologic examination was performed using von Kossa stain to identify AMiC. We compared all‐cause and cardiovascular mortality between patients with and without AMiC. The mean follow‐up was 37.8 ± 34.5 months, and AMiC was present in 38.8% (n = 57) of patients. The presence of diabetes (odds ratio: 16.49, 95% confidence interval: 1.81–150.36, P = 0.013) was the only independent risk factor for vascular access AMiC. During the observational period, there were 27 cardiovascular deaths. Kaplan–Meier analysis showed an increased cardiovascular mortality risk (log rank = 4.83, P = 0.028) in AMiC patients, and Cox regression analysis confirmed that AMiC was an independent predictor for cardiovascular mortality (hazard ratio: 2.35, 95% confidence interval: 1.09–5.09, P = 0.030). In conclusion, vascular access AMiC is a strong risk factor for cardiovascular mortality in HD patients.     

Integration of clinical and imaging data to predict death in hemodialysis patients

In a prior publication, we demonstrated that a model integrating clinical and simple imaging data predicted the presence and severity of coronary artery calcification in prevalent hemodialysis patients. Herein we report the ability of the same model to predict all‐cause death. We assessed all‐cause mortality in 141 consecutive maintenance hemodialysis patients from two dialysis centers followed for a median of 79 months from enrollment. Patients were risk stratified according to a simple cardiovascular calcification index (CCI) that included patient's age, dialysis vintage, calcification of the cardiac valves, and abdominal aorta. The mean patients’ age was 55 ± 14 years. Abdominal aorta calcification was present in 57% of the patients, and 44% and 38% had aortic and mitral valve calcification, respectively. During follow‐up, 75 deaths (93 deaths per 1000 person‐years) were recorded. The CCI was linearly associated with risk of death, such that the unadjusted hazard risk (HR) increased by 12% for each point increase in CCI (P < 0.001). Further adjustments for age, sex, study center, diabetes mellitus, history of cardiovascular disease, hypertension, congestive heart failure, left ventricular hypertrophy, systolic, and diastolic blood pressure did not substantially change the strength of this association (HR 1.10; 95%CI: 1.00–1.21; P = 0.03). The CCI is a simple clinical model that can be used to risk stratify maintenance hemodialysis patients.     

Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.     

Changes in circulating biomarkers during a single hemodialysis session

The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular‐sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration‐induced hemoconcentration. Among vascular calcification‐related biomarkers, osteoprotegerin and fetuin‐A remained unchanged while fibroblast growth factor‐23 (FGF23) decreased by ?19%. Changes of FGF23 and changes of phosphate correlated (ρ = 0.61, P < 0.001). While C‐reactive protein did not change, interleukin‐6 (IL‐6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL‐6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC‐related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF‐23 and phosphate during HD warrants further studies.     

Poor correlation between coronary artery calcification and obstructive coronary artery disease in an end-stage renal disease patient

Vascular calcification is highly prevalent and often severe in patients with chronic kidney disease. Arterial calcification in patients with chronic kidney disease can result from the deposition of mineral along the intimal layer of arteries in conjunction with atheromatous plaques or from calcium deposition in the medial wall of arteries, also known as Monckeberg's sclerosis. Whether coronary artery calcium scores as measured by electron beam computed tomography correlate with occlusive atherosclerotic disease in the dialysis population is uncertain. Here we report a case of an asymptomatic patient with diabetes mellitus and end-stage renal disease undergoing maintenance hemodialysis, who was found to have extremely elevated coronary artery calcium scores on electron beam computed tomography, but varied degrees of atherosclerotic plaque in her coronary arteries on coronary angiography. This suggests that in addition to the calcification anticipated in a remodeled intima, a proportion of the calcification is also likely to be in the arterial media. Thus, this case demonstrates that even an extremely high coronary calcium score may not be a satisfactory surrogate marker for obstructive atherosclerosis in elderly diabetic dialysis patients.     

Association of coronary artery calcium score and vascular dysfunction in long‐term hemodialysis patients

Long‐term hemodialysis patients are prone to an exceptionally high burden of cardiovascular disease and mortality. The novel temperature‐based technology of digital thermal monitoring (DTM) of vascular reactivity appears associated with the severity of coronary artery disease in asymptomatic population. We hypothesized that in hemodialysis patients, the DTM and coronary artery calcium (CAC) score have a gradient association that follows that of subjects without kidney disease. We examined the cross‐sectional DTM‐CAC associations in a group of long‐term hemodialysis patients, and their 1:1 matched normal counterpart. Area under the curve for temperature (TMP‐AUC), the surrogate of the DTM index of vascular function, was assessed after a 5‐minute arm‐cuff reactive hyperemia test. Coronary calcium score was measured via electron beam computed tomography or multidetector computed tomography scan. We studied 105 randomly recruited hemodialysis patients (age: 58 ± 13 years, 47% men) and 105 age‐ and gender‐matched controls. In hemodialysis patients vs. controls, TMP‐AUC was significantly worse (114 ± 72 vs. 143 ± 80, P = 0.001) and CAC score was higher (525 ± 425 vs. 240 ± 332, P < 0.001). Hemodialysis patients were 14 times more likely to have CAC score >1000 as compared with controls. After adjustment for known confounders, the relative risk for case vs. control for each standard deviation decrease in TMP‐AUC was 1.46 (95% confidence interval: 1.12–1.93, P = 0.007). Vascular reactivity measured via the novel DTM technology is incrementally worse across CAC scores in hemodialysis patients, in whom both measures are even worse than their age‐ and gender‐matched controls. The DTM technology may offer a convenient and radiation‐free approach to risk‐stratify hemodialysis patients.