Impact of Dysmagnesemia on Atrial Fibrillation in Maintenance Hemodialysis Patients: A Nationwide Study.

INTRODUCTION: The dose-response relationship between serum magnesium (sMg) and atrial fibrillation (AF) and the contribution of dysmagnesemia to AF among hemodialysis patients remain unknown. Hence, we examined the dose-response correlation between sMg and AF and estimated the extent of the contribution of dysmagnesemia to AF in this population. METHODS: This was a nationwide cross-sectional study on the Japanese Society for Dialysis Therapy registry, also known as Japanese Renal Data Registry (JRDR), encompassing a nationwide population of dialysis centers, as of the end of 2019. Eligible participants were adult patients undergoing hemodialysis three times per week. The main exposure was sMg, categorized into seven categories (≤1.5, >1.5-≤2, >2-≤2.5, >2.5-≤3, >3-≤3.5, >3.5-≤4, and ≥4.0 mg/dL). The outcome was AF reported by dialysis facilities. The independent contribution to AF was assessed via logistic regression to generate population-attributable fractions, assuming a causal relationship between sMg and AF. RESULTS: Total 165,926 patients from 2,549 facilities were investigated. AF prevalence was 7.9%. Compared with the reference (>2.5-≤3 mg/dL), lower sMg was associated with increased AF (adjusted odds ratios (ORs) (95% confidence interval, CI) of 1.49 (1.19-1.85), 1.24 (1.17-1.32), and 1.11 (1.06-1.16) for sMg of ≤1.5, >1.5-≤2.0, and >2.0-≤2.5 mg/dL categories, respectively). Elevated sMg was associated with fewer AF (adjusted OR 0.87 [95% CI, 0.79-0.96] for sMg of >3.0-≤3.5 mg/dL). The adjusted population-attributable fraction of lower sMg and higher and lower sMg for AF was 7.4% and 6.9%, respectively. An association did indeed exist between lower sMg and AF, with the lowest percentages of AF at sMg levels above the reference range for the general population. CONCLUSION: Dysmagnesemia may be an important contributor to AF among adult hemodialysis patients. Further, longitudinal studies are warranted to determine whether sMg correction reduces the AF incidence.

Effect of atherosclerosis on the relationship between atrial fibrillation and ischemic stroke incidence among patients on hemodialysis.

In patients undergoing hemodialysis, the impact of atrial fibrillation (AF) through cardiac thromboembolism on the development of ischemic stroke may be influenced by the severity of atherosclerosis present. However, there are no large-scale reports confirming whether the severity of atherosclerosis influences the relationship between AF and stroke development in patients requiring hemodialysis. We aimed to investigate the effects of atherosclerotic disease on the relationship between AF and new-onset ischemic stroke. This nationwide longitudinal study based on dialysis facilities across Japan used data collected from the Japanese Renal Data Registry at the end of 2019 and 2020. The exposure was AF at the end of 2019, identified using a resting 12-lead electrocardiography. The primary outcome was the incidence of cerebral infarction (CI) after 1 year. To examine whether the number of atherosclerotic diseases modified the association between AF and the outcome, we estimated the odds ratios (ORs) using a logistic regression model and then assessed the presence of global interaction using Wald test. Following the study criteria, data from 151,350 patients (mean age, 69 years; men, 65.2%; diabetic patients, 48.7%) were included in the final analysis. A total of 9841 patients had AF (prevalence, 6.5%). Between 2019 and 2020, 4967 patients (3.2%) developed ischemic stroke. The adjusted OR of AF for new-onset CI was 1.5, which showed a decreasing trend with an increasing number of atherosclerotic diseases; the interaction was not significant (P = 0.34). While age, diabetes mellitus, smoking, systolic blood pressure, and serum C-reactive protein concentration were positively associated with CI, intradialytic weight gain, body mass index, and serum albumin level were negatively associated. While we demonstrated the association between AF and new-onset CI among Japanese patients on hemodialysis, we failed to demonstrate the evidence that the association was attenuated with an increasing numbers of atherosclerotic complications.

Trust, Multidimensional Health Literacy, and Medication Adherence among Patients Undergoing Long-Term Hemodialysis.

BACKGROUND: Basic health literacy and trust in physicians can influence medication adherence in patients receiving dialysis. However, how high-order health literacy is associated with medication adherence and how trust in physicians mediates this association remain unclear. We assessed the inter-relationships between health literacy, trust in physicians, and medication adherence. We investigated the mediating role of trust in physicians in the relationship between health literacy and medication adherence. METHODS: This multicenter cross-sectional study included Japanese adults receiving outpatient hemodialysis at six dialysis centers. Multidimensional health literacy was measured using the 14-item Functional, Communicative, and Critical Health Literacy scale. Trust in physicians was measured using the five-item Wake Forest Physician Trust scale. Medication adherence was measured using the 12-item Adherence Starts with Knowledge scale. A series of general linear models were created to analyze the associations between health literacy and Adherence Starts Knowledge scores with and without trust in physicians. Mediation analysis was performed to determine whether trust in physicians mediated this association. RESULTS: In total, 455 patients were analyzed. Higher functional and communicative health literacies were associated with less adherence difficulties (per 1-point higher: -1.79 [95% confidence interval (CI): -2.59 to -0.99] and -2.21 [95% CI: -3.45 to -0.96], respectively), whereas higher critical health literacy was associated with greater adherence difficulties (per 1-point higher: 1.69 [95% CI: 0.44 to 2.94]). After controlling for trust in physicians, the magnitude of the association between health literacies and medication adherence decreased. Trust in physicians partially mediated the association between functional or communicative health literacy and medication adherence (especially beliefs) and completely mediated the association between critical health literacy and medication adherence (especially behaviors). CONCLUSIONS: Functional and communicative health literacies were positively associated with medication adherence, whereas critical health literacy was negatively associated with it. Each association was mediated by trust in physicians.

Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study.

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI-estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI-all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.

Effects of Bovine Lactoferrin on the Maintenance of Respiratory and Systemic Physical Conditions in Healthy Adults-A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: We investigated the effects of bovine lactoferrin (LF) on the maintenance of the respiratory and systemic physical conditions. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Healthy adults at Kyushu University of Health and Welfare ingested a placebo or bovine LF (200 mg/day) for 12 weeks. The primary endpoints were the total respiratory and systemic symptom scores. The secondary endpoint was the activity of plasmacytoid dendritic cells (pDCs) in peripheral blood. RESULTS: A total of 157 subjects were randomized (placebo, n = 79; LF, n = 78), of whom, 12 dropped out. The remaining 145 participants were included in the full analysis set (placebo group, n = 77; LF group, n = 68). The total scores for respiratory and systemic symptoms during the intervention were significantly lower in the LF group than in the placebo group. The expression of CD86 and HLA-DR on pDCs was significantly higher in the LF group than in the placebo group at week 12. Adverse events were comparable between the groups, and no adverse drug reactions were observed. CONCLUSIONS: These results suggest that orally ingested LF supports the normal immune system via maintaining pDC activity, and maintains respiratory and systemic physical conditions in healthy adults.

Takotsubo cardiomyopathy after vaccination for coronavirus disease 2019 in a patient on maintenance hemodialysis.

Coronavirus disease-2019 (COVID-19) has affected more than 220 million individuals since the global pandemic began. There is an urgent need for safe and effective vaccines, and vaccinations, such as mRNA vaccines, have been initiated worldwide. However, the adverse effects of these vaccines remain unclear. We herein present a case of an 80-year-old female on maintenance hemodialysis who developed takotsubo cardiomyopathy 4 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. There was no obvious trigger for the onset of takotsubo cardiomyopathy other than the COVID-19 vaccination, which was the most significant event preceding her presentation. Echocardiograms obtained during her admission allowed us to monitor and show the recovery of left ventricular wall motion. We confirmed the diagnosis of takotsubo cardiomyopathy based on the findings, including transient left ventricular dysfunction, electrocardiographic abnormalities, an elevated troponin level, and the absence of occlusive coronary artery disease. In the present case, the vaccination may have triggered emotional or physical stress. Although difficulties are associated with proving the causal relationship in the present case, the temporal relationship between the vaccination and the onset of takotsubo cardiomyopathy is highly suggestive. The adverse effects associated with the vaccine are typical of COVID-19 vaccines administered to date, most of which are acceptable. Therefore, despite our experience of the present case, we still recommend the vaccination for COVID-19 because takotsubo cardiomyopathy induced by the COVID-19 vaccine is extremely rare and the prognosis of the patient was good. We herein present the first case of a patient on hemodialysis who developed takotsubo cardiomyopathy after receiving COVID-19 vaccination.

Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study.

BACKGROUND: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. METHODS: Study design: cohort study. SETTING: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. PREDICTOR: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. OUTCOMES: all-cause mortality and hospitalization during the mean 2.8-year follow-up. MEASUREMENTS: hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. RESULTS: The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. CONCLUSIONS: PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.

Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients.

BACKGROUND: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. METHODS: This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. RESULTS: Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. CONCLUSION: Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.

Synergic Impact of Body Mass Index, Diabetes, and Age on Long-Term Mortality in Japanese Incident Hemodialysis Patients: A Cohort Study on a Large National Dialysis Registry.

OBJECTIVES: The relationships among body mass index (BMI), diabetes, age, and all-cause mortality in hemodialysis patients remain unclear. We examined BMI-stratified relationships between diabetes, age, and the risk of long-term mortality in incident hemodialysis patients. METHODS: This is a cohort study. Data were obtained from the national dialysis registry in Japan 2007 that included 35,415 incident hemodialysis patients and 6,061 patients aged ≥20 years with BMI data. Patients were divided into 6 categories according to baseline BMI (low: <18.5, normal: 18.5-25, Obesity: ≥25) and the presence or absence of diabetes. The primary outcome was all-cause mortality during a 5-year follow-up. Hazard ratios were estimated using Cox's model for the relationships among diabetes, BMI categories, and all-cause mortality, and adjusted for potential confounders. Patients with a normal BMI and non-diabetic were the reference category. We also examined the effects of age on these relationships. RESULTS: A total of 6,061 patients, including 3,239 with diabetes, were enrolled. During the follow-up, 31.0% and 30.7% of all and diabetic patients, respectively, died. Cox's regression analysis showed that low BMI, but not obesity, was independently associated with an increased risk of all-cause death in patients with and without diabetes. When patients were divided into 2 groups-younger and older than 60 years-the risk of mortality in both groups was increased in low BMI with diabetes. CONCLUSIONS: Among Japanese incident hemodialysis patients, low BMI increases the risk of all-cause mortality. The markedly high mortality rate in diabetic patients with low BMI regardless of age warrants attention.

Characterisation of N-terminal pro-brain natriuretic peptide in dialysis patients and its reduced prognostic significance in the elderly.

Characterisation of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic haemodialysis patients and its prognostic significance in age stratification have not been addressed. A prospective cohort study with cross-sectional analyses at baseline was performed. Outcomes were all-cause mortality, non-malignancy-related mortality, and cardiovascular disease (CVD)-related mortality. NT-proBNP was significantly higher in elderly, female, and low dry weight patients. Study patients were divided into two groups: Group-O (≥75 years) and Group-Y (<75 years). The 7-year follow-up receiver operating curve analysis showed that NT-proBNP significantly predicted all outcomes. All-cause mortality cut-off points were significantly different among the groups (total cohort, 5375 pg/mL; Group-Y, 3682 pg/mL; Group-O, 11750 pg/mL). Cox regression analysis showed risks for all outcomes by tertile NT-proBNP significantly higher in the total cohort and Group-Y as adjusted by potential confounders. For all-cause mortality, hazard ratios and 95% confidence intervals (CI) were T2 1.70 (0.89 to 3.25), p = 0.11, T3 2.95 (1.54 to 5.67), p < 0.01 in Group-Y; and T2 1.00 (0.64 to 1.58), p = 1.00; T3 1.50 (0.94 to 2.40), p = 0.09 in Group-O. In conclusion, NT-proBNP was significantly higher in elderly, female, and low dry weight chronic dialysis patients. NT-proBNP was significantly associated with all outcomes. However, this association was reduced in elderly patients.

Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study.

BACKGROUND/AIMS: Uric acid (UA) levels are affected by changes in dialysis; however, the relationship between the pre- and postdialysis UA difference (UAD) and mortality remains unclear. METHODS: A total of 1,073 patients receiving maintenance hemodialysis (HD) were enrolled in this cohort study and followed up for 5 years. Patients were divided into quartile categories according to baseline UAD. Cox's regression analyses were used to investigate the relationship between UAD categories and all-cause and cardiovascular (CV) mortalities while adjusting for potential confounders. RESULTS: A total of 280 patients died of all causes, including 121 CV deaths, during the follow-up. In the analysis for all-cause mortality, hazard ratios were significantly higher in the lowest UAD group (< 4.7 mg/dL) than in the highest UAD group (> 6.2 mg/dL). A correlation was not observed with CV mortality. CONCLUSION: UAD correlated with all-cause mortality. UAD may be the most appropriate reference for controlling UA in HD patients.

Grading of Left Ventricular Diastolic Dysfunction with Preserved Systolic Function by the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Recommendations Contributes to Predicting Cardiovascular Events in Hemodialysis Patients.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) causes heart failure with a preserved left ventricular ejection fraction (LVEF) in the general population. OBJECTIVE: To examine the relationships between the LVDD grades of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) recommendations and several arteriosclerotic parameters and major cardiovascular events (MACE) in hemodialysis patients with preserved LVEF. METHOD: Sixty-three prevalent hemodialysis patients (median age [interquartile range], 69 [64-75] years, 31.7% female) with normal systolic function (LVEF > 50%) were enrolled. LVDD evaluated by echocardiography at baseline was divided into three groups according to ASE/EACVI recommendations (normal diastolic function [ND], n = 24; intermediate, n = 19; diastolic dysfunction [DD], n = 20). All patients underwent analyses of several arteriosclerotic parameters (carotid intima-media thickness [CIMT], plaque score [PS], ankle brachial index [ABI], and brachial-ankle pulse wave velocity [baPWV]). The presence or absence of postdialysis orthostatic hypotension was assessed in each dialysis session. MACE during the 1-year follow-up period was obtained from medical records. Kaplan-Meier and Cox's regression analyses were used to investigate the relationship between LVDD grades and MACE. RESULTS: Postdialysis orthostatic hypotension and PS, but not CIMT, ABI, or baPWV, increased proportionally with LVDD grades. Eleven patients developed MACE, including 2 cardiovascular deaths. The Kaplan-Meier analysis showed that MACE frequently occurred in the DD grade (p = 0.002 by the log-rank test). Cox's regression analysis adjusted for potential confounders (age, sex, diabetes, systolic blood pressure, and body mass index) revealed that the DD grade was associated with MACE when the ND grade was set as a reference. CONCLUSIONS: In maintenance hemodialysis patients with normal ventricular systolic function, a classification of LVDD by the 2016 ASE/EACVI recommendations may be a useful tool for predicting cardiovascular events.

Diminishing dry weight is strongly associated with all-cause mortality among long-term maintenance prevalent dialysis patients.

OBJECTIVES: To investigate the relationship between dry weight (DW) change and survival in long-term maintenance prevalent dialysis patients. METHODS: We conducted a prospective data collection study with retrospective analysis of the registered data. Patients were followed up for 5 years (1-year observation of DW changes and subsequent 4-year follow-up). The outcome was all-cause mortality. The predictors were 1-year DW change rates. The hazard ratios (HRs) for all-cause mortality were calculated using multivariable Cox regression analysis, fully adjusted for age, sex, basal kidney disease, dialysis vintage, current smoking, past cardiovascular events, serum albumin, DW at enrollment, serum creatinine, mean predialysis systolic blood pressure, and cardiothoracic ratio or 1-year cardiothoracic ratio change rate. Propensity score (PS) analysis was also conducted using the same covariates of Cox regression analysis. RESULTS: In total, 899 dialysis patients (mean dialysis vintage: 101.2 months) were followed up, and 180 deaths were recorded, of which 90 were of cardiovascular origin. Each 2% decrement of DW showed adjusted HR, and the 95% confidence interval was 1.24 [1.16-1.33]. According to the 1-year DW change rate, participants were divided into five groups (group A, ≥+3%; group B, +1 to +2.9%; group C, -0.9 to +0.9%; group D, -2.9 to -1.0%; and group E, ≤-3%). For survival curves based on grouping, group B had the best and group E had the worst survival rate (p<0.01, log-rank test). Therefore, we set group B as a reference; adjusted risks for death of groups D and E were 2.16 [1.23-3.79] and 2.66 [1.54-4.58], respectively. However, this relation was blunted in patients of heavier DW. The PS-matched cohort showed a poorer prognosis in patients with diminishing DW divided by DW change rate at -0.635% (mean value of DW change rate). CONCLUSION: In the long-term maintenance hemodialysis cohort, 1-year DW decrement, especially ≤-3.0%, was significantly associated with all-cause mortality, and cardiovascular disease-related death was prominent in these patients.

N-terminal-pro-B-type-natriuretic peptide associated with 2-year mortality from both cardiovascular and non-cardiovascular origins in prevalent chronic hemodialysis patients.

N-terminal-pro-B-type-natriuretic peptide (NT-proBNP) was a predictive marker of cardiovascular disease (CVD)-related death in chronic dialysis patients. NT-proBNP was also correlated with markers of inflammation, malnutrition and protein-energy wasting. We hypothesized whether NT-proBNP was also associated with non-CVD death in chronic dialysis patients. A prospective observational study for incidence of death in chronic dialysis patients was conducted. Prevalent chronic dialysis patients (n = 1310) were enrolled and followed for 24 months. One hundred forty-four deaths were recorded. Area under the curve using ROC analysis for NT-proBNP showed: all causes of death (0.761), CVD-related (0.750), infection and malignancy-related (0.702) and others and unknown (0.745). After adjusting for age, sex, hemodialysis vintage, cardiothoracic ratio, mean pre-dialysis systolic blood pressure, dry weight and basal kidney disease, the hazard ratios (95% confidence intervals) per 1-log NT-proBNP calculated using multivariate Cox analysis were: all causes of death, 3.83 (2.51-5.85); CVD-related, 4.30 (2.12-8.75); infection and malignancy-related, 2.41 (1.17-4.93); and others and unknown origin, 5.63 (2.57-12.37). NT-proBNP was significantly associated not only with CVD-relate but also with non-CVD-related deaths in this population of prevalent chronic dialysis patients.

Relationship between Hemoglobin Levels Corrected by Interdialytic Weight Gain and Mortality in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study.

BACKGROUND: Although hemoglobin (Hb) levels are affected by a change in the body fluid status, the relationship between Hb levels and mortality while taking interdialytic weight gain (IDWG) at blood sampling into account has not yet been examined in hemodialysis patients. STUDY DESIGN: Cohort study. SETTING, PARTICIPANTS: Data from the Miyazaki Dialysis cohort study, including 1375 prevalent hemodialysis patients (median age (interquartile range), 69 (60-77) years, 42.3% female). PREDICTOR: Patients were divided into 5 categories according to baseline Hb levels and two groups based on the median value of IDWG rates at blood sampling at pre-HD on the first dialysis session of the week. OUTCOMES: All-cause and cardiovascular mortalities during a 3-year follow-up. MEASUREMENTS: Hazard ratios were estimated using a Cox model for the relationship between Hb categories and mortality, and adjusted for potential confounders such as age, sex, dialysis duration, erythropoiesis-stimulating agent dosage, Kt/V, comorbid conditions, anti-hypertensive drug use, serum albumin, serum C-reactive protein, serum ferritin, and serum intact parathyroid hormone. Patients with Hb levels of 9-9.9 g/dL were set as our reference category. RESULTS: A total of 246 patients (18%) died of all-cause mortality, including 112 cardiovascular deaths. Lower Hb levels (<9.0g/dL) were associated with all-cause mortality (adjusted HRs 2.043 [95% CI, 1.347-3.009]), while Hb levels were not associated with cardiovascular mortality. When patients were divided into two groups using the median value of IDWG rates (high IDWG, ≥5.4% and low IDWG, <5.4%), the correlation between lower Hb levels and all-cause mortality disappeared in high IDWG patients, but was maintained in low IDWG patients (adjusted HRs 3.058 [95% CI,1.575-5.934]). On the other hand, higher Hb levels (≥12g/dL) were associated with cardiovascular mortality in high IDWG patients (adjusted HRs 2.724 [95% CI, 1.010-7.349]), but not in low IDWG patients. CONCLUSION: In hemodialysis patients, target Hb levels may need to be selected in consideration of IDWG at blood sampling.

Risk of Cerebral Infarction in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study (MID study).

BACKGROUND/AIMS: Predictors including the preventive effects of antiplatelet and anticoagulant drugs on cerebral infarction (CI) events have not yet been clarified in dialysis patients. The aim of the present study was to examine the risk of CI and preventive effects of these drugs in Japanese hemodialysis patients. METHODS: Patients receiving maintenance hemodialysis (n=1,551, median age (interquartile range), 69.0 (59.0-78.0) years; 41.5% female) were enrolled in the Miyazaki Dialysis Cohort Study and prospectively followed-up for 3 years. Kaplan-Meier and Cox's regression analyses were used to clarify the risk of CI. RESULTS: Eighty-four patients developed CI at an incidence of 21.5/1000 patients per year. The presence of a previous history of CI, atrial fibrillation (AF), and diabetes mellitus in addition to age were also identified as predictive factors for new CI, whereas no relationship was observed between antiplatelet and/or anticoagulant usage and CI. Furthermore, no significant difference was noted in the frequency of CI events between patients with AF who received warfarin and those who did not. CONCLUSIONS: The incidence of CI was higher in dialysis patients with a previous history of CI and AF; however, the preventive effects of antiplatelet/anticoagulant drugs on the development of CI were not evident.

Apoprotein B/Apoprotein A-1 Ratio and Mortality among Prevalent Dialysis Patients.

BACKGROUND AND OBJECTIVES: In dialysis patients, the associations between apoprotein profile and all-cause or cardiovascular disease (CVD)-related mortality are not well known. We, therefore, investigated whether apoprotein levels are associated with these events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We undertook a prospective observational cohort study of prevalent hemodialysis patients aged ≥18 years (n=1081), who were followed for 4 years (2011-2014). Outcomes were all-cause and CVD-related mortality. Predictors used were baseline apoprotein levels, particularly the apoprotein B (apo B)/ apoprotein A-1 (apo A-1) ratio. A Cox regression analysis was used to calculate the hazard ratios (HRs) for mortality. Apo A-1, apo B, and apo B/ apo A-1 ratio were analyzed with adjustments in three models: model 1, basic adjustment for age and sex; model 2, basic adjustments plus dialysis conditions (dialysis vintage, mean predialysis systolic blood pressure, dry weight, and mean intradialytic weight gain); and model 3, model 2 plus metabolic and inflammatory conditions (basal kidney disease, serum albumin, C-reactive protein level, and statin use). RESULTS: Of the 1081 patients included in the study, 203 deaths were recorded, 92 of which were related to CVD. The apo B/ apo A-1 ratio was significantly associated with all-cause and CVD-related mortality when analyzed by 1-SD increments or quartile IV versus I in all models. In model 3, HRs and 95% confidence intervals (95% CIs) for 1-SD increments of apo B/ apo A-1 ratio for all-cause mortality or CVD-related mortality were: HR, 1.16 (95% CI, 1.00 to 1.35), or HR, 1.38 (95% CI, 1.11 to 1.71), respectively, and for quartile IV versus I: HR, 1.65 (95% CI, 1.05 to 2.57), or HR, 2.56 (95% CI, 1.21 to 5.40), respectively. Apo A-1 was significantly associated with both mortalities in models 1 and 2. However, apo B was only significantly associated with CVD-related mortality in model 3. CONCLUSIONS: Apoprotein measurement, especially the apo B/ apo A-1 ratio, was significantly associated with all-cause and CVD-related mortality in prevalent dialysis patients.

Glycaemic control is a predictor of infection-related hospitalization on haemodialysis patients: Miyazaki Dialysis Cohort study (MID study).

AIM: Although infection is the second leading cause of death in maintenance haemodialysis patients, the effects of glycaemic control on infection in diabetic haemodialysis patients have not yet been examined in detail. We examined the relationship between diabetes or glycemic control and infection-related hospitalization (IRH) in haemodialysis patients. METHODS: Patients receiving maintenance haemodialysis (n = 1551, 493 diabetic patients) were enrolled in this prospective cohort study in December 2009 and followed-up for 3 years. IRH during the follow-up period was abstracted from medical records. Kaplan-Meier and Cox regression analyses were used to investigate the relationship between diabetes or glycaemic control and IRH. RESULTS: The Kaplan-Meier analysis revealed that the risk of IRH was significantly higher in haemodialysis patients with diabetes, particularly in those with poorly controlled HbA1c levels (HbA1c ≥ 7.0%), than in haemodialysis patients without diabetes. When patients with ≥HbA1c 7.0% were divided into two groups using a median value of HbA1c, the risk of IRH was significantly higher in those with the poorest glycaemic control (HbA1c ≥ 7.4%), an older age, or lower albumin levels. The multivariable-adjusted hazard ratio for the risk of IRH was not higher in the second criteria of HbA1c (HbA1c 7.0-7.3%), but was significantly higher in the group with the poorest glycaemic control (HbA1c ≥ 7.4%) than in those in the good control criterion (HbA1c < 7.0%). CONCLUSIONS: Although diabetes is a risk factor for IRH among maintenance haemodialysis patients, the relationship between glycaemic control and the risk of infection is not linear. Therefore, the risk of infection may increase in a manner that is dependent on the glycaemic control threshold.

Prognostic Implication of Three-Dimensional Mitral Valve Tenting Geometry in Dilated Cardiomyopathy.

BACKGROUND AND AIM OF THE STUDY: Functional mitral regurgitation (FMR) is a clinically important complication of left ventricular (LV) dysfunction, occurring as a result of geometric deformity in the mitral valve (MV) complex. The study aim was to determine whether tenting parameters derived from real-time three-dimensional echocardiography (RT3DE) can predict the long-term prognosis for patients with dilated cardiomyopathy (DCM). METHODS: Mitral valve tenting morphology, LV volume and function, and papillary muscle positions were monitored using transthoracic RT3DE in 75 subjects (66 with DCM, nine controls). The maximum tenting sites of the leaflet (maxTS) were also mapped from the reconstructed 3D images, to determine if the 3D tenting parameters correlated to long-term outcome. RESULTS: Follow up information was collected from 62 patients with DCM over a mean period of 42 +/- 31 months. Cardiovascular events occurred in 30 patients (48%), including 13 cardiac deaths (21%). The patients were allocated to an Event group (n = 30) or a Non-event group (n = 32). The LV volumes were significantly larger and LV ejection fraction was lower in the Event group compared to the Non-event group. The 3D tenting volumes were significantly larger in the Event group than the Non- event group (p = 0.05). The maxTS were positioned mostly in the middle portion of the anterior mitral leaflet in the Non-event group (maxTS-mid AML), but in the Event group they were mostly found in the MV coaptation region of the leaflet (maxTS-coapt) (p <0.001). Patients with maxTS-coapt had a worse prognosis compared to those with maxTS-mid AML. On multivariate Cox regression analysis, maxTS was the strongest predictor of event-free survival. CONCLUSION: The 3D tenting pattern, assessed with RT3DE, would be an important clinical parameter in predicting long-term prognosis in patients with DCM.