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.     

Achieving targets for bone and mineral metabolism: the impact of cinacalcet HCl in clinical practice

Achieving the K/DOQI targets for bone and mineral metabolism has proven difficult with the use of vitamin D analogues and phosphate binders. The introduction of cinacalcet HCl provided a new tool with a novel therapeutic mechanism of action. The purpose of this study was to evaluate the effect of the introduction of combination algorithm for managing secondary hyperparathyroidism (SHPT) on phosphorus, calcium, and biointact parathyroid hormone (PTH). The 61 patients who dialyzed in the facility from January 2004 (baseline) and who remained in the facility as of April 2005 (follow-up) were included in the study. In the baseline period, 37 (61%) of the patients received paricalcitol at some time during the 3-month observation period. In the follow-up period, 19% or 31% of the patients received cinacalcet HCl. Of those not receiving cinacalcet HCl, 67% had PTH at or below target, 17% were felt to be noncompliant with oral meds, 7% had low calcium, and 10% either could not get the medication or were not switched to the combination pathway. Compared with the baseline period, the percent of patients who met the PTH target increased from 19.7% to 37.7%, p<0.05. The percent of patients meeting all 4 targets increased from 14.8% to 24.6%, although this did not reach statistical significance. The introduction of cinacalcet HCl into a treatment algorithm for management of SHPT resulted in a significant increase in the percentage of patients achieving the PTH target while maintaining the other mineral metabolism targets.     

Mortality differences among organisms causing septicemia in hemodialysis patients

Septicemia is a serious problem in hemodialysis patients because it can lead to life-threatening complications and a persistently elevated risk of death. Most analyses have not examined whether there are differences in mortality risk among the organisms that cause these episodes of septicemia. This study was a retrospective cohort analysis of first septicemia hospitalizations during the first year of hemodialysis. Time to death (both in-hospital and within 12 weeks post-discharge) was compared among the different septicemia-causing organisms based on discharge diagnoses in Medicare billing data from 1996 to 2001. The effect of various complications on mortality risk was also evaluated. There were 22,130 septicemia hospitalizations identified. The most common organism identified was Staphylococcus aureus (27%), with no other organism having an incidence >10%. The overall unadjusted death rate from admission through 12 weeks of follow-up was 34%. During the first hospitalization, the death rate was 14%, and during the 12-week period after the hospitalization it was 20%. In adjusted analyses, S. aureus was associated with a 20% higher risk of death both during the in-hospital period and the 12-week post-discharge period, when compared with all other specified organisms. Hospitalizations complicated by meningitis, stroke, or endocarditis were also associated with increased risk of mortality, independent of the organism causing septicemia. Septicemia hospitalizations are associated with a high mortality rate--both during the initial hospitalization and after discharge. Meningitis, stroke, and endocarditis represent particularly serious complications. Overall, septicemia hospitalizations (especially for S. aureus) are serious events, and patients would benefit from better treatment and prevention.     

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.     

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.     

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD 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.     

Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all‐cause mortality in hemodialysis patients: A prospective cohort study

Introduction: Patients with chronic kidney disease, especially those with end‐stage renal disease, have an increased risk of death. Previous studies have suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR) has not been evaluated in HD patients. In this study, we prospectively studied the predictive value of MLR for all‐cause and cardiovascular mortality in HD patients and compared it with NLR. Methods: Patients who had been on a HD treatment for at least 6 months were enrolled. MLR was calculated by dividing the monocyte count by the lymphocyte count. Survival outcomes were estimated using the Kaplan‐Meier method and compared by the log‐rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of MLR and other clinical factors on all‐cause and cardiovascular mortality. Results: Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65, 7.02, and 11.15, respectively per 100 patient‐years. The Kaplan‐Meier analysis revealed that survival rates were significantly different among three MLR groups (P < 0.001). In multivariate Cox regression analyses, MLR was independently associated with all‐cause mortality (HR 4.842; 95% CI, 2.091–11.214; P < 0.001) and cardiovascular mortality (HR 6.985, 95% CI 1.943–25.115, P = 0.003) as continuous variables. NLR was not an independent predictor of all‐cause nor cardiovascular mortality after adjusted with MLR. Conclusions: The main finding of the study suggest that higher MLR was a strong and independent predictor of all‐cause and cardiovascular mortality and overwhelmed NLR among HD patients.     

Determinants of metabolic acidosis among hemodialysis patients

Metabolic acidosis is frequently present, poorly controlled, and associated with adverse effects among hemodialysis patients. Potential determinants of metabolic acidosis include endogenous acid production, administration of alkali, neutralization of acid by buffers, dilution of serum bicarbonate by interdialytic fluid gain, and loss of bicarbonate in stool. Understanding the relative importance of these determinants may help guide efforts to manage metabolic acidosis. We used chart abstraction, patient interviews, and laboratory testing to assess variables related to acid production (protein breakdown), alkali administration (dialysis dose, missed treatments, dialysate bicarbonate concentration, oral bicarbonate supplements), acid buffering (phosphorus binders), dilution of bicarbonate (interdialytic weight gain), and loss of bicarbonate in stool (diarrhea) for 190 randomly selected patients from 44 hemodialysis facilities. We used multivariate analyses to determine which potential determinants were independently associated with predialysis serum bicarbonate levels. Of all patients, 30% had metabolic acidosis (serum bicarbonate level <22 mEq/L). On multivariate analysis, metabolic acidosis was more likely with increased protein nitrogen appearance (odds ratio [OR] 1.60 per 0.2 g/kg/day, p=0.001) and less likely with increased Kt/V (OR 0.61 per 0.20 increase in Kt/V, p<0.001) and with increased calcium carbonate use (OR 0.38 per 2 g/day, p=0.003). Key determinants of metabolic acidosis among hemodialysis patients are protein breakdown, dialysis dose, and specific phosphorus binders. Further work is needed to develop interventions to address these determinants.     

Comparison of B-type natriuretic peptide and NT proBNP as predictors of survival in patients on high-flux hemodialysis and hemodiafiltration

End stage renal failure is associated with very high risk of cardiovascular disease. Serum levels of B-type natriuretic peptide (BNP) and NT proBNP reflect cardiovascular risk but it is unknown which of these peptides is a better predictor of survival in this population. BNP and NT proBNP levels and other relevant parameters were measured in 103 patients on high-flux hemodialysis (HD) and hemodiafiltration. Patients were followed for 4 years or until transplantation or death. Median BNP level was 262 pg/mL while the corresponding NT proBNP level was 362 pg/mL. Levels of these peptides were significantly lower in patients receiving hemodiafiltration than in those on high-flux HD. Only 1 of the 26 patients with normal NT proBNP died during follow-up while 3 of the 33 patients with normal BNP levels died in the same period. Both median BNP and NT proBNP levels were higher in those who died during follow-up than in those who survived 4 years. Cox Proportional Hazard models showed that both logBNP and log NT proBNP were independent predictors of survival. The area under the receiver operating characteristic curve was very similar for BNP and NT proBNP (0.779 vs. 0.781) for predicting 4-year survival. Net reclassification improvement analysis showed that adding NT proBNP to the baseline model lead to improved prediction of 4-year survival. BNP and NT proBNP levels were markedly elevated in HD patients and were highly predictive of survival. NT proBNP may have marginal advantage over BNP in predicting survival in this population.     

Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients

Vascular calcification is associated with a poor prognosis in dialysis patients. It can be assessed with computed tomography but simple inoffice techniques may provide useful information. We compared the results obtained with a simple noninvasive technique with those obtained using multidetector computed tomography for aortic arch calcification volume (AoACV) in chronic hemodialysis (HD) patients. The enrolled study subjects were 63 (32 men and 31 women) maintenance HD patients. Calcification of the aortic arch was semiquantitatively estimated with a AoAC score (AoACS) on plain chest radiology. The AoACV was increased, with a mean value of 6.6 ranging from 0% to 36.5%. The coefficient of intraobserver variation was less than 2.5%. Aortic arch calcification score was highly correlated with AoACV (r=0.635, P<0.001). Multiple regression analysis showed age (F value=12.62, P<0.001) and pulse pressure (F value=4.54, P=0.037) to be significant independent determinants of AoACS. In conclusion, a simple measurement of AoACS may be useful for inoffice imaging to choose a therapeutic regimen in HD patients.     

Association between afebrile status and in‐hospital mortality among adult chronic hemodialysis patients with bacteremia

Aim: We aimed to compare the in‐hospital mortality between febrile and afebrile chronic hemodialysis (HD) patients with bacteremia and analyze the blood culture positive rate according to the C‐reactive protein (CRP) level. Methods: We collected data from 2006 to 2014. One hundred ninety bacteremic events were assigned to the “febrile group” (n = 162) and “afebrile group” (n = 28) based on the presence of fever. Fever was defined as a tympanic temperature >37.5°C or axillary temperature >37.0°C. Results: In‐hospital mortality (41.4% vs. 6.1%) was higher; and the interval between admission and blood culture was longer (3 vs. 1 h) in the afebrile group than in the febrile group. The mean reason for blood culture in the afebrile group was a high CRP level. Conclusions: An afebrile status in HD patients with bacteremia is associated with higher in‐hospital mortality. Blood culture and empirical antibiotic administration, irrespective of the fever status, should be considered in HD patients with a CRP ≥ 5 mg/dL.     

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.