Alirocumab in a high cardiovascular risk patient on hemodialysis with liver abnormalities

We present a male diabetic type 2 patient on hemodialysis (HD) with high cardiovascular (CVD) risk and hyperlipidemia. The patient was under cholesterol‐lowering therapy with statin and ezetimibe but he was obligated to discontinue due to chronic hepatitis C virus infection. Statins and ezetimibe may exert a potential hepatotoxic effect and for this reason, we attempted to find an alternative treatment to prevent CVD. Given that a potential hepatotoxic effect has not been reported for Abs SPCK9, we administered alirocumab 150 mg every 2 weeks for a total of 8 weeks. Low‐density lipoprotein levels have decreased and no side effects have been observed. In conclusion, alirocumab is a safe and efficient alternative therapy approach for HD patients with high CVD risk and liver abnormalities. We suggest that SPCK 9 inhibitors should be considered as a first line treatment for lowering cholesterol in this specific patient group.     

Effects of music on complications during hemodialysis for chronic renal failure patients

The study was planned as a case‐control study to examine the effects of music on some of the complications experienced by chronic renal failure (CRF) patients during hemodialysis. A total of 60 patients (30 intervention and 30 control) diagnosed with end‐stage renal failure undergoing hemodialysis treatment participated in this study. The study was conducted in Manisa Merkez Efendi State Hospital Hemodialysis Unit and Manisa Özel Anemon Hemodialysis between April 2012 and July 2012. The intervention group listened 30 minutes in each session (12 total sessions) Turkish art music at the beginning of the third hour of their hemodialysis sessions. Patient Information Form and visual analog scale to assess pain, nausea, vomiting, and cramps during hemodialysis session were used. For the analysis of data, the number, percentage, chi‐square test, and significance test of independent group differences between two averages were conducted. According to the findings of the study, the average of the intervention and control group ages, respectively, was 50.86 ± 11.3 and 55.13 ± 9.68. The primary duration of hemodialysis treatment for both intervention and control groups was “1 year and above” (70.0%). The intervention group's pain and nausea scores were lower than the control group for all 12 sessions. The difference between the intervention and the control group's pain scores was significant (P < 0.05). However, in pain scores from the first session to 12th session, continuous decreasing trend was not observed. According to the results, music can be used as an independent nursing practice for reduction of complications for CRF patients receiving hemodialysis treatment.     

Predictors of cardiovascular events in hemodialysis patients after stress myocardial perfusion imaging

Cardiovascular prognosis in patients under normal stress myocardial perfusion images (MPI) is generally excellent. However, this is not true for patients with chronic kidney disease (CKD) treated by hemodialysis. This study evaluated prognostic factors of adverse cardiovascular events in hemodialysis patients in whom stress MPI was performed. Pharmacological stress MPI was performed in 88 hemodialysis patients, and we retrospectively followed‐up for 26 months. Cardiovascular events included cardiac death, nonfatal myocardial infarction, and unstable angina. Cardiovascular events occurred in 16 patients (18%). Univariate Cox regression analysis revealed that peripheral artery disease (PAD) and parameters of stress MPI were significant predictors of cardiovascular events. Multivariate Cox regression analysis revealed that only PAD (hazard ratio = 6.54; P = 0.002), and abnormal stress MPI (hazard ratio = 8.26; P = 0.008) were independent and significant predictors of cardiovascular events. Kaplan–Meier analysis showed better prognosis in patients with normal stress MPI than in patients with abnormal stress MPI (P < 0.001, log–rank test). However, in patients with normal stress MPI, cardiovascular events occurred in 10 of the 76 patients (13%). Among patients with normal stress MPI, Kaplan–Meier analysis showed that patients with no PAD had better prognosis than patients with PAD (P = 0.001, log–rank test). In hemodialysis patients, both PAD and stress MPI were powerful cardiovascular predictors. Normal stress MPI alone cannot guarantee good prognosis in terms of cardiovascular events. Consideration of PAD may improve the predictive value of stress MPI in some patients.     

Correlation between conjunctival and corneal calcification and cardiovascular calcification in patients undergoing maintenance hemodialysis

The purpose of this study was to investigate the correlation of conjunctival and corneal calcification (CCC) with cardiovascular calcification in patients undergoing maintenance hemodialysis (MHD). A total of 122 patients undergoing MHD in our hospital were included in this study. Conjunctival and corneal calcification was examined by slit lamp and graded. Abdominal aortic calcification (AAC), aortic valve calcification (AVC), and mitral valve calcification (MVC) were determined by X‐ray or ultrasound. The correlation of CCC with AAC, AVC, and MVC was analyzed. Biochemical, hematological, and cardiovascular data were compared between patients with different severity of CCC or AAC. Mitral valve calcification was significantly associated with AAC in our patients. Conjunctival and corneal calcification positively correlated with AAC. We also found that patients with severe CCC exhibited significantly higher levels of serum calcium, phosphate, product of calcium and phosphate, serum copper, cystatin, intact parathyroid hormone, and vitamin D than patients with mild CCC. In addition to significantly increased levels of serum calcium, product of calcium and phosphate, serum copper, and cystatin, patients with severe AAC also had higher high‐sensitivity C‐reactive protein level and greater left ventricular posterior wall thickness and left ventricular end‐diastolic interventricular septum thickness than patients with mild AAC. Our results suggest that patients undergoing MHD with severe CCC or AAC have high degree of mineral metabolism disorder, inflammation, and cardiovascular function disorder. The strong correlation between CCC and AAC indicates that CCC score might be used as an indirect indicator to predict cardiovascular risks in patients undergoing MHD.     

Differences in cardiovascular mortality rates among hemodialysis patients in the United States and Japan: The importance of background cardiovascular mortality

Mortality rates among hemodialysis patients differ greatly among the United States, Europe, and Japan and it has been hypothesized that this is mainly due to differences in practice patterns. Results from the international DOPPS study, however, indicate that differences in practice patterns among the United States, Japan, and Europe are small and not alone explanatory for the differences in mortality rates. Ethnic variability in predisposition to atherosclerotic cardiovascular disease in the general population may lead to significant differences in background cardiovascular mortality in the United States, Japan, and Europe. It is our hypothesis that cardiovascular mortality in dialysis patients is to a great extent dependent on cardiovascular background mortality of the general population. We are currently studying the relationship between all‐cause and cardiovascular death rates in countries worldwide using the WHO database. Preliminary data from 35 countries show that all‐cause and cardiovascular death rates differ significantly among regions, with Eastern European countries reporting four‐ to sevenfold higher death rates than Asian countries. A strong linear relationship between cardiovascular and all‐cause death rates is observed among these countries. The next step of our study will be to compare country‐specific cardiovascular death rates of dialysis populations with those of the respective general populations. Ethnic differences in cardiovascular morbidity and mortality may be explained by genetic variability based upon polymorphism of genes involved in the pathogenesis of atherosclerosis and myocardial infarction.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Influence of sodium profile in preventing complications during hemodialysis

Although a safe procedure, hemodialysis (HD) can cause numerous complications. The objective of this study was to evaluate the incidence of complications during dialysis, interdialytic weight gain, and the predialysis and postdialysis blood pressure in HD patients with and without variable sodium. Patients were observed during 12 HD sessions and those presenting with recurrent hypotension were selected for a step-wise model of variable sodium profiling. A total of 53 patients were evaluated; the mean-SD age was 53.7+/-16.3 years and 22 (41.5%) were male. Of these, 18 (34.0%) were selected to receive variable sodium profiling: the mean (SD) age was 59.9+/-12.6 years, and 10 (55.6%) were female. A significant decline in the occurrence of cramps (p<0.027), in the mean interdialytic weight gain (p<0.009), and a tendency to reduce the number of hypotensive episodes were detected in patients using variable sodium profiling. On the other hand, predialysis systolic blood pressure presented a significant increase (p<0.048). Using variable sodium, there was a statistically significant reduction in cramps and in the mean interdialytic weight gain. There was a significant increase in predialysis systolic pressure. Regarding hypotension episodes, only a tendency toward a reduction in the frequency of hypotension episodes could be detected.     

Relationship between erythropoietin resistance index and left ventricular mass and function and cardiovascular events in patients on chronic hemodialysis

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight-adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow-up period was 53 months. The Kaplan-Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log-rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04-8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.     

Left ventricular assist device patient maintained on home hemodialysis: A novel class of patients to the home dialysis population

Severe heart failure is increasingly being managed by cardiac transplantation, and in some cases mechanical support devices serve as destination therapies. Left ventricular assist devices (LVADs) were approved for destination therapy for end stage heart failure patients before the more advanced total artificial heart modality became available. One common complication of mechanical assist device placement is acute kidney injury. Historically, patients with mechanical support devices have had to have inpatient hemodialysis until combined heart kidney transplant. Though, some units have started accepting LVAD patients in outpatient dialysis clinics. The cost of in center hemodialysis remains high and home dialysis modalities are becoming increasingly popular. We report the first patient with an LVAD to undergo training and successful home hemodialysis while awaiting combined heart kidney transplantation.     

Complications of home hemodialysis

Home hemodialysis is regaining popularity as a treatment choice for end-stage kidney disease. This trend is fueled by numerous reports of better survival and improved quality of life with primarily home-based more frequent and/or longer hours of hemodialysis. Home hemodialysis in the contemporary era is generally very safe. Advances in machine technology have reduced technical complications and longer and more frequent treatments have reduced the risk of hypotension and cardiovascular instability. A successful home hemodialysis program must focus on patient safety to prevent serious hemorrhage from needle dislodgement and enable an aseptic cannulation technique. In addition, vigilance in relation to machine maintenance procedures and attention to water quality are key skills that patients must acquire for optimal outcomes. The possibility of increased septic events with longer and more frequent hemodialysis regimens performed in the home, the long-term psychosocial effects of home hemodialysis, and the best methods for maintaining compliance of patients in the long term are of particular contemporary interest.     

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.     

The impact of extended-hours home hemodialysis and buttonhole cannulation technique on hospitalization rates for septic events related to dialysis access

Few studies adequately document adverse events in patients receiving long, slow, and overnight hemodialysis (NHD). Concerns about high rates of dialysis access complications have been raised. This is an observational cohort study comparing hospital admission rates for vascular access complications between alternate nightly NHD (n=63) and conventional hemodialysis (n=172) patients established on chronic hemodialysis for at least 3 months. Overall, hospital admission rates and hospital admission rates for cardiac and all infective events are also reported. The NHD cohort was younger and less likely to be female, diabetic, or have ischemic heart disease than the conventional hemodialysis cohort. When NHD and buttonhole cannulation technique were used simultaneously, there was a demonstrated increased risk of septic dialysis access events: incidence rate ratio 3.0 (95% confidence interval 1.04-8.66) (P=0.04). The majority of blood culture isolates in NHD patients were gram-positive organisms, particularly Staphylococcus aureus. Alternate nightly NHD did not significantly change total hospital admissions or hospital admissions for indications other than dialysis access complications, compared with conventional hemodialysis. Our data suggest that buttonhole cannulation technique should be used with caution in patients performing extended-hours hemodialysis as this combination appears to increase the risk of septic access complications. Randomized-controlled trials are needed to confirm these findings.     

Dipyridamole stress echocardiography in diagnosis and prognosis of hemodialysis patients with asymptomatic coronary disease

The prevalence of coronary artery disease (CAD) is high in hemodialysis (HD) patients. The aim of the study was to assess the diagnostic and prognostic value of dipyridamole stress echocardiography (DSE) in nondiabetic HD patients without signs or symptoms of CAD. In 51 out of 158 evaluated HD patients (21 females, age 67 [33–85] years, HD duration 38 [9–271] months), resting echocardiography and DSE were performed. Exclusion criteria were known CAD, diabetes mellitus, and pulmonary and oncologic pathologies. Logistic regression analysis was carried out to identify predictors of abnormal DSE response, while Cox regression analysis was performed to determine variables associated with total and cardiovascular mortality, after 43.3 (11–60) months of follow‐up. Seven patients (14%) showed a positive response to DSE (DSE+). In 5/7, CAD was documented by angiography: All of them underwent coronary revascularization. DSE+ patients had significantly smaller body mass index than patients with a negative response (DSE‐): 21.7 ± 1.9 vs. 25.1 ± 3.4 kg/m² (p = 0.018). During follow‐up, 16 (31%) patients died. Older age hazard ratio [HR = 1.07; confidence interval (CI) = 1.01–1.12; p = 0.02] and higher plasma phosphate levels (HR = 10.41; CI = 2.30–47.17; p < 0.01) were predictors of total mortality. Male gender (HR = 22.7; CI = 1.45–354.4; p = 0.03), older age (HR = 1.24; CI = 1.03–1.50; p = 0.02), longer HD duration (HR = 1.13; CI = 1.01–1.26; p = 0.04), and positive response to DSE (HR = 5.82; CI = 1.04–32.65; p = 0.04) were associated with cardiovascular mortality. Ten percent of asymptomatic HD patients had significant CAD, but timely diagnosis did not seem to improve their prognosis. Total survival was associated with age and higher levels of plasma phosphate, while male gender, older age, longer HD duration, and DSE+ were predictors of cardiovascular mortality.     

Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients

Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross‐sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA‐IR) and hemodialysis dose by single‐pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (β = 0.590, P < 0.001), waist circumference (β = 0.572, P < 0.001), body fat mass (β = 0.562, P < 0.001), percentage of body fat mass (β = 0.408, P = 0.003), percentage of lean tissue mass (β = ?0.421, P = 0.002), LV mass (β = 0.426, P = 0.002), carotis intima media thickness (β = 0.289, P = 0.042), triglyceride/high‐density lipoprotein cholesterol ratio (β = 0.529, P < 0.001), 1/HOMA‐IR (β = ?0.386, P = 0.006), and spKt/V (β = ?0.311, P = 0.028). No association was exhibited with visfatin C, high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor‐alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high‐density lipoprotein cholesterol ratio, HOMA‐IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.     

Modification of cardiovascular risk in hemodialysis patients: an evidence-based review

Cardiovascular disease accounts for 40% to 50% of deaths in dialysis populations. Overall, the risk of cardiac mortality is 10-fold to 20-fold greater in dialysis patients than in age and sex-matched controls without chronic kidney disease. The aim of this paper is to review critically the evidence that cardiac outcomes in dialysis patients are modified by cardiovascular risk factor interventions. There is limited, but as yet inconclusive controlled trial evidence that cardiovascular outcomes in dialysis populations may be improved by antioxidants (vitamin E or acetylcysteine), ensuring that hemoglobin levels do not exceed 120 g/L (especially in the setting of known cardiovascular disease), prescribing carvedilol in the setting of dilated cardiomyopathy, and by using cinacalcet in uncontrolled secondary hyperparathyroidism. Similarly, there are a number of negative controlled trials, which have demonstrated that statins, high-dose folic acid, angiotensin-converting enzyme inhibitors, multiple risk factor intervention via multidisciplinary clinics, and high-dose or high-flux dialysis are ineffective in preventing cardiovascular disease. Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of chronic kidney disease or because the pathogenesis of cardiovascular disease in dialysis patients is different from that in the general population. Large, well-conducted, multicenter randomized-controlled trials in this area are urgently required.     

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.