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Aim: In patients with end-stage kidney disease (ESKD), it is unclear whether an imbalance between myocardial oxygen supply and demand leads to myocardial injury (MI). This study clarifies the association between the balance of the rate pressure product (RPP), consisting of the systolic blood pressure multiplied by the pulse rate (PR), a marker for myocardial oxygen demand, and hemoglobin (Hb), a marker for oxygen supply, with MI., Methods: A total of 283 consecutive unselected patients for hemodialysis were enrolled in this retrospective, cross-sectional study, and were divided into four groups according to Hb levels (high or low) and RPP. Potential imbalances between myocardial oxygen supply and demand were defined as patients with simultaneous high RPP and low Hb levels. The odds ratio (OR) for MI, defined as cardiac troponin T (cTnT) of ≥ 0.15 ng/mL was investigated using logistic regression analysis between the four patient groups., Results: The mean age was 68.7 years, 71.3% were men, and 52.6% had diabetes. The mean Hb level was 9.0 g/dL, and 20.5% of patients were latently diagnosed with MI. The median RPP and cTnT level was 12,144 and 0.083 ng/mL, respectively. When exposed to simultaneous high RPP with low Hb, OR significantly increased compared with that of the well-balanced group (RPP ＜12,500 and Hb ≥ 9.0 g/dL; OR 3.63, p＜0.05). Similar results were obtained in multivariate analysis after adjusting for confounding variables. These associations were enhanced or weakened when the Hb cut-off level became lower (Hb=8 g/dL) or higher (Hb=10 g/dL)., Conclusions: As the myocardial oxygen supply and demand balance in patients with ESKD is potentially associated with MI, appropriate management for blood pressure, PR, and anemia may prevent MI.

Introduction: QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation., Methods: A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome., Results: A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve., Conclusion: Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

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., (© 2024. Crown.)

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., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rationale & Objective: Despite α-blockers' use for hypertension as add-on therapy in patients treated with hemodialysis, scant information is available on their association, particularly with safety, in these patients., Study Design: Prospective cohort study., Setting & Participants: patients treated with hemodialysis and receiving antihypertensive agents in the Japan Dialysis Outcomes and Practice Patterns Study, phases 4-6, were analyzed., Exposure: Primary exposure was the prescription of α-blocking antihypertensive agents at baseline., Outcomes: Incident fractures, falls, and all-cause mortality., Analytical Approach: Multivariable Cox and modified Poisson regression analysis., Results: Of 5,149 patients treated with hemodialysis (mean age, 65 years; 68% men) receiving antihypertensive drugs, 717 (14%) received α-blocking agents. During a mean follow-up period of 2.0 years, 247 fractures, 525 falls, and 498 deaths occurred. Multivariable analysis showed no significant association of α-blocker use and increased risk of fractures (hazard ratio [HR], 0.92 [95% confidence interval {CI}, 0.61-1.38]), falls (HR, 0.94 [95% CI, 0.74-1.20]), or all-cause deaths (HR, 0.87 [95% CI, 0.64-1.20]) compared with α-blocker nonuse. α-Blocker use was, however, significantly associated with a decreased risk of all-cause mortality in the subgroup analysis, for example, patients who were older (HR, 0.71 [95% CI, 0.51-0.99]), were women (HR, 0.68 [95% CI, 0.48-0.95]), or reported a history of cardiovascular disease (HR, 0.67 [95% CI, 0.48-0.95]) or a predialysis blood pressure of ≥140 mm Hg (HR, 0.69 [95% CI, 0.49-0.98])., Limitations: Selection bias cannot be ruled out given the prevalent user analysis., Conclusions: No significant association between α-blocker use and the risk of worse safety-related outcomes was seen, indicating that clinicians may safely prescribe α-blockers to patients receiving hemodialysis who require blood pressure lowering., Plain-Language Summary: α-Blockers have been generally reserved for use as add-on therapy for resistant or refractory hypertension. However, little is known about the safety of α-blockers in patients treated by hemodialysis. We analyzed 5,149 patients receiving hemodialysis in Japan who were receiving antihypertensive drugs from the Japan Dialysis Outcomes and Practice Patterns Study. The results showed no significant increase in the risk of fractures, falls, or deaths for patients using α-blockers compared with those who did not, suggesting that α-blockers may be safely prescribed for patients receiving hemodialysis who need to lower their blood pressure., (© 2023 The Authors.)

Background: Responsiveness to erythropoiesis-stimulating agents (ESAs) has been reported to be associated with increased cardiovascular disease (CVD) and mortality in patients undergoing hemodialysis (HD). However, the association between hyporesponsiveness to the long-acting ESA, epoetin beta pegol (CERA), and CVD remains unknown., Methods: This multicenter prospective study included 4034 patients undergoing maintenance HD. After shifting from prior ESA to CERA, we studied the association between erythropoietin resistance index (ERI) at six months and outcomes, including cardiac events, major adverse cardiovascular events (MACE), and all-cause mortality, using Cox proportional hazards models (Landmark analyses) and marginal structural models to adjust for time-dependent confounding factors, including iron-containing medications and hemodiafiltration (HDF)., Results: The median dialysis vintage and the observational period were 5.0 years and 22.1 months, respectively. The landmark analyses revealed that the highest tertile of baseline ERI (T3) was associated with a significantly higher all-cause mortality than the lowest tertile (T1) (hazard ratio [HR]: 1.48, 95% CI: 1.03-2.13). Furthermore, marginal structural models revealed that time-dependent ERI T3 was significantly associated with increased cardiac events (HR: 1.59, 95% CI: 1.14-2.23), MACE (HR: 1.60, 95% CI: 1.19-2.15), all-cause mortality (HR: 1.97, 95% CI: 1.40-2.77), and heart failure (HF) (HR: 2.05, 95% CI: 1.23-3.40) compared to T1. A linear mixed effects model showed that iron-containing medications and HDF are negatively associated with time-dependent ERI., Conclusions: Baseline ERI at six months predicted only all-cause mortality; however, time-dependent ERI was a predictor of cardiac events, all-cause mortality, MACE, and HF. The widespread use of iron-containing medications and HDF would ameliorate ESA hyporesponsiveness., Competing Interests: Declaration of Competing Interest H. F. received speaker fees as honoraria from Chugai and Kyowa Kirin, advisory board fees as honoraria from Chugai, and scholarship grants from Chugai and Kyowa Kirin. T. H. received speaker fees as honoraria from Chugai, Kyowa Kirin, Kissei, Ono, Torii, Otsuka, Bayer, Asahi Kasei and Astellas; grants from Chugai, Kyowa Kirin, Kissei, Ono, Torii, Otsuka, Terumo, Fuso, Bayer, Asahi Kasei, Eisai, and Takeda; advisory board fees as honoraria from Kyowa Kirin, Ono, Glaxo SmithKline and Astellas. K. T. received speaker fees as honoraria from Chugai, Kyowa Kirin, Otsuka, Ono and Bayer; grants from Chugai, Kyowa Kirin, Otsuka, Ono, Kissei, Baxter and Tanabe Mitsubishi; and advisory board fees as honoraria from Chugai, Kissei, and Sanwa. T. K. received speaker fees as honoraria from Chugai and Kyowa Kirin. N. J. received speaker fees as honoraria from Chugai, Kyowa Kirin and Torii, and grants from Chugai, Kyowa Kirin and Torii. K. T. received speaker fees as honoraria from Chugai and Kyowa Kirin and grants from Chugai and Kyowa Kirin. H. H. received speaker fees as honoraria from Chugai, Kissei, Torii, Tanabe Mitsubishi and Astellas. Y. U. received speaker fees as honoraria from Chugai. K. N. received speaker fees as honoraria from Chugai and Kyowa Kirin and grants from Chugai and Kyowa Kirin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Natriuretic peptides are associated with malnutrition and volume overload. Over-hydration cannot simply be explained by excess extracellular water in patients undergoing hemodialysis. We assessed the relationship between the extracellular and intracellular water (ECW/ICW) ratio, N -terminal pro-B-type natriuretic peptide (NT-proBNP), human atrial natriuretic peptide (hANP), and echocardiographic findings. Body composition was examined by segmental multi-frequency bioelectrical impedance analysis in 368 patients undergoing maintenance dialysis (261 men and 107 women; mean age, 65 ± 12 years). Patients with higher ECW/ICW ratio quartiles tended to be older, were on dialysis longer, and had higher post-dialysis blood pressure and lower body mass index, ultrafiltration volume, serum albumin, blood urea nitrogen, and creatinine levels ( p < 0.05). The ECW/ICW ratio significantly increased with decreasing ICW, but not with ECW. Patients with a higher ECW/ICW ratio and lower percent fat had significantly higher natriuretic peptide levels. After adjusting for covariates, the ECW/ICW ratio remained an independent associated factor for natriuretic peptides (β = 0.34, p < 0.001 for NT-proBNP and β = 0.40, p < 0.001 for hANP) and the left ventricular mass index (β = 0.20, p = 0.002). The ICW-ECW volume imbalance regulated by decreased cell mass may explain the reserve capacity for fluid accumulation in patients undergoing hemodialysis.

Purpose: To determine the location of coronary atherosclerosis distribution observed in patients with chronic kidney disease (CKD)., Methods: A cross-sectional study was conducted using the database of cardiovascular medicine data from Saitama Sekishinkai Hospital to clarify the association between renal function and angiographic characteristics of coronary atherosclerosis. In total, 3268 patients who underwent percutaneous coronary intervention were included. Propensity score matching revised the total to 1772. The association of renal function with the location and/or distribution of coronary atherosclerosis lesions was then examined., Results: Overall, coronary lesion was observed in the left anterior descending coronary artery (LAD) in 56% patients, whereas 28% and 22% were in the right coronary artery (RCA) and left circumflex coronary artery (LCX), respectively. LAD was most affected and observed in 57% patients with stage 1 CKD. RCA was second-most affected, at 26% CKD stage 1, but it increased to 31%, 38%, and 59% in CKD 3, 4, and 5, respectively. In CKD 5 patients, the RCA was the most affected artery (59%), with 41% LAD lesions. Logistic regression analysis after propensity score matching showed that the odds ratios for an RCA lesion was 3.658 in CKD 5 ( p  = .025) compared with CKD 1 after adjusting for traditional risk factors., Conclusion: The prevalence of RCA lesions, but not LAD or LCX lesions, increased with increasing CKD stage. The pathophysiology of coronary atherosclerosis may differ by lesion location. Deterioration of renal function may affect progression of atherosclerosis more in the RCA than in the LAD or LCX.

Background: Although multidisciplinary care (MDC) is necessary for controlling chronic kidney disease (CKD), its impact on compliance with management target values in the CKD guidelines remains unclear. This study was designed to clarify the relationship between compliance with management target values and renal prognosis in CKD outpatients who received MDC., Methods: There were 255 outpatients with pre-dialysis CKD who received MDC. Achievement rates of systolic, and diastolic blood pressure, hemoglobin, uric acid, low-density lipoprotein cholesterol, and hemoglobin A1c values determined according to CKD guidelines were compared before and 12 months after MDC. In addition, after dividing achievement rates of the target values at 12 months after MDC into four groups (A < 30% ≤ B < 60% ≤ C < 80% ≤ D), dialysis initiation and renal survival rates were compared., Results: There was a significant increase in the overall achievement rate from 62.8 to 69.1% (p < 0.001). The higher the achievement rate after MDC, the lower the dialysis initiation rate (A 72.7%, B 35.3%, C 20.5%, D 8.2%, p < 0.001). There was also a significantly higher renal survival rate (p < 0.001). These findings suggest that MDC for CKD raised awareness of health literacy, and improved the achievement rate of target values. Furthermore, the higher the achievement rate, the later the initiation of dialysis, which led to improvement of renal survival., Conclusions: MDC can improve compliance with management target values for CKD, suggesting that it may improve renal prognosis., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: The aim of comprehensive multidisciplinary care (MDC) by the chronic kidney disease (CKD) team is not only to prevent worsening renal function, but also provide education on the selection of renal replacement therapy (RRT) by shared decision making (SDM). The purpose of this study was to examine the effects of MDC for predialysis outpatients on dialysis therapy, especially with regard to peritoneal dialysis (PD)., Methods: This study evaluated 112 CKD patients who underwent dialysis at our hospital starting from 2012, with 53 outpatients receiving MDC from the CKD team and 59 outpatients not receiving MDC. Annual decreases in the estimated glomerular filtration rates (ΔeGFR), the duration from the time of intervention to dialysis initiation, the urgent dialysis rate using a temporary catheter, and the PD selection rate were compared and examined between the two groups. The ΔeGFR, the duration from intervention to PD initiation, and the PD retention rate were compared between 18 PD patients in the MDC group and 10 PD patients in the non-MDC group., Results: The MDC group had a significantly lower ΔeGFR, significantly longer duration, and a significantly lower urgent dialysis initiation rate versus the non-MDC group. Moreover, there was a significantly higher PD selection rate, significantly prolonged duration, and significantly higher PD retention rate., Conclusions: Multidisciplinary CKD team care for outpatients is effective in delaying the progression of CKD and avoiding the initiation of urgent dialysis; contributing to improved PD selectivity and continuity by SDM.

The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m 2 . The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.

Background: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease., Methods: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models., Results: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05-1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01-1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05-1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137-140 mEq/L) and the lowest ΔSNa (≤2 mEq/L)., Conclusions: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Recent studies have reported that high mean corpuscular volume (MCV) might be associated with mortality in patients with advanced chronic kidney disease (CKD). However, the question of whether a high MCV confers a risk for mortality in Japanese patients remains unclear. We conducted a longitudinal analysis of a cohort of 8571 patients using data derived from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 1 to 5. Associations of all-cause mortality, vascular events, and hospitalization due to infection with baseline MCV were examined via Cox proportional hazard models. Non-linear relationships between MCV and these outcomes were examined using restricted cubic spline analyses. Associations between time-varying MCV and these outcomes were also examined as sensitivity analyses. Cox proportional hazard models showed a significant association of low MCV (< 90 fL), but not for high MCV (102 < fL), with a higher incidence of all-cause mortality and hospitalization due to infection compared with 94 ≤ MCV < 98 fL (reference). Cubic spline analysis indicated a graphically U-shaped association between baseline MCV and all-cause mortality (p for non-linearity p < 0.001). In conclusion, a low rather than high MCV might be associated with increased risk for all-cause mortality and hospitalization due to infection among Japanese patients on hemodialysis.

Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (≥100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low β2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term., Competing Interests: Takeshi Nakanishi declares having grants from Chugai Pharmaceutical, Takeda Pharmaceutical Company, and Kyowa Kirin and received a speaker fee from Chugai Pharmaceutical and Kyowa Kirin. None of the grants to Takeshi Nakanishi were used in this study. Takahiro Kuragano declares having grants from Chugai Pharmaceutical, Pharmaceutical Company, Ono Pharmaceutical Co., LTD, Kissei Pharmaceutical Co., LTD, and Kyowa Kirin and received a speaker fee from Kyowa Kirin, Fuso Pharmaceutical Industries, Ltd., and Bayer Yakuhin, LTD. None of the grants to Takahiro Kuragano were used in this study. Takahiro Kuragano also received an advisory board fee from Astellas Pharma Inc and Astellas Pharma Inc. Nobuhiko Joki declares having received honoraria as a speaker from Chugai Pharmaceutical, Roche Diagnostics and Kyowa Kirin. Hiroki Hase declares having received honoraria as a speaker from Chugai Pharmaceutical and Kyowa Kirin. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Patients with end-stage renal disease (ESRD) treated with hemodialysis suffer a high burden of poor functional status. Poor functional status is known as a strong, consistent predictor of mortality. However, little is known about the trajectory of functional status and its association with clinical outcomes in the ESRD population. We examined the association between a change in the functional status over time and all-cause mortality among patients on hemodialysis., Design and Methods: This was a prospective cohort study of 817 patients with ESRD on hemodialysis with repeat measures of functional status, who enrolled in the Japan Dialysis Outcomes and Practice Patterns Study phase V. The functional status was assessed based on the Katz Index and Lawton-Brody instrumental activities of daily living scale, and the assessments were conducted twice over a median of 361 (range: 339-378) days between 2012 and 2013. We classified patients into 2 groups based on having or not having at least a 1-point decline in the functional status score. To evaluate the association between the decline in the functional status and all-cause mortality with adjustment for potential confounders, a Cox regression analysis was conducted., Results: Over the study period, 19.9% of the patients showed a decline in the functional status score. During the follow-up period, 44 (5.4%) patients died. Using the Cox regression analysis and adjusting for potential confounders, it was determined that the decline in functional status score was significantly associated with higher mortality (incidence rate: 2.2 vs. 7.0 per 100 person-years; adjusted hazard ratio: 2.68; 95% confidence interval: 1.31-5.50)., Conclusions: The present study provides evidence that ESRD patients on hemodialysis demonstrating a decline in the functional status are at elevated risk of mortality. Our findings strengthen the evidence underpinning the importance of interventions to maintain the functional status in this vulnerable population., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Comprehensive education about lifestyle, nutrition, medications and other types of treatment is important to prevent renal dysfunction in patients with chronic kidney disease (CKD). However, the effectiveness of multidisciplinary care on CKD progression has not been evaluated in detail. We aimed to determine whether multidisciplinary care at our hospital could help prevent worsening renal function associated with CKD., Methods: A total of 150 pre-dialysis CKD outpatients accompanied (n = 68) or not (n = 82) with diabetes mellitus (DM) were enrolled into this study. We assessed annual decreases in estimated glomerular filtration rates (ΔeGFR), and measured systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin (Hb), uric acid (UA), low-density lipoprotein cholesterol (LDL), hemoglobin A1c (HbA1c) values and urinary protein to creatinine ratios (UPCR) 12 months before and after multidisciplinary care. In addition, changes in the number of medications and prescription ratio before and after multidisciplinary care were assessed in 90 patients with CKD who could confirm their prescribed medications., Results: The ΔeGFR significantly improved between before and after multidisciplinary care from - 5.46 to - 0.56 mL/min/1.73 m 2 /year, respectively. The number of medications and prescription ratio showed no significant changes before and after multidisciplinary care. The ratios of improved ΔeGFR were found in 66.7% of all patients, comprising 63.1% of males and 76.9% of females, 64.8% without DM and 69.4% with DM. Values for UA, LDL, and HbA1c were significantly reduced among patients with improved ΔeGFR., Conclusion: Comprehensive multidisciplinary care of outpatients might help prevent worsening renal function among patients with CKD.

Background: Myocardial perfusion imaging (MPI) is considered useful for risk stratification among patients with chronic kidney disease (CKD), without renal deterioration by contrast media., Methods and Results: The Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS 3) is a multicenter, prospective cohort study investigating the ability of MPI to predict cardiac events in 529 CKD patients without a definitive coronary artery disease. All patients were assessed by stress and rest MPI with 99m Tc-tetrofosmin and data were analyzed using a defect scoring method and QGS software. Major cardiac events were analyzed for 3 years after registration. The mean eGFR was 29.0 ± 12.8 (mL/minute/1.73 m 2 ). The mean summed stress/rest/difference (SSS, SRS, SDS) scores were 1.9 ± 3.8, 1.1 ± 3.0, and 0.8 ± 1.8, respectively. A total of 60 cardiac events (three cardiac deaths, six sudden deaths, five nonfatal myocardial infarctions, 46 hospitalization cases for heart failure) occurred. The event-free survival rate was lower among patients with kidney dysfunction, higher SSS, and higher CRP values. Multivariate Cox regression analysis independently associated SSS ≥8, eGFR <15 (mL/minute/1.73 m 2 ), and CRP ≥0.3 (mg/dL) with cardiac events., Conclusions: Together with eGFR and CRP, MPI can predict cardiac events in patients with CKD.

Background: There is no obvious evidence regarding biological variation of procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The aim of this study was to determine the within- and between-person biological variation of PCT levels in HD patients without infections., Methods: A multicenter, prospective, cohort study enrolled 123 HD patients without any signs of infectious disease. Baseline PCT levels were determined pre- and post-HD, and then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and 24 weeks after baseline blood-sampling, regardless of the presence or absence of infectious disease. Analytical variation (CVa), the within-person biological variation (CVi), between-person biological variation (CVb), individual index (II), and the reference change value (RCV) were calculated., Results: The mean age was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD was 87 months. The median value for baseline pre-HD PCT was 0.23 ng/mL, which is much higher than the reference level for healthy individuals. PCT levels decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II was 0.46, and RCV was calculated as 96.4% with 99% probability., Conclusions: The PCT level was significantly higher in stable HD patients without manifest bacterial infection. CVb was more variable than CVi in HD patients, which indicates that relative change is more important than absolute PCT levels for diagnosing bacterial infection, and doubling or more of the baseline PCT level may imply the presence of a bacterial infection in HD patients.

Objectives: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD., Design and Methods: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL., Results: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent., Conclusions: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background/aims: There is lack of definitive evidence about the association between erythropoiesis-stimulating agent (ESA) responsiveness in the pre-dialysis phase and mortality. Therefore, we conducted a hospital-based, retrospective, cohort study to assess the predictive value of ESA response for prognosis in incident hemodialysis patients., Methods: A total of 108 patients without preexisting cardiovascular disease who had been started on maintenance hemodialysis were studied. ESA responsiveness just before starting dialysis was estimated using an erythropoietin resistance index (ERI). The endpoint was defined as all-cause death., Results: During a mean follow-up period of 3.1 ± 1.6 years, 18 (17%) patients died. Overall, the multivariate Cox regression analysis revealed that the log-transformed ERI remained an independent predictor of all-cause death after adjustment using a propensity score (hazard ratio 2.25, 95% CI 1.25-4.06)., Conclusions: Among incident hemodialysis patients, hyporesponsiveness to ESA may be associated with mortality., (© 2019 S. Karger AG, Basel.)

Fluid volume overload is common and is associated with adverse outcomes in hemodialysis patients. Practicing physicians individually manage fluid volume balance in their dialysis patients according to blood pressure, interdialytic weight gain, cardiac function, nutritional status, and other comorbidities. However, accurate assessment of fluid volume status remains a concern. Indicators of dry weight target have been explored further with newer concepts and technologies. In general, total body water comprises approximately 50%-60% of adult body weight (range, 45%-75%), and water comprises 73.3% of lean body mass. The standard hydration status between intracellular water and extracellular water is maintained at a ratio of 62:38 in healthy adults, which, however, is influenced universally by body cell volume driven by age and muscle mass. Fluid volume imbalance in dialysis patients also is characterized primarily by decreased body cell mass associated with aging and muscle attenuation, as well as excess extracellular water content associated with sodium retention, which may be associated with the reserve capacity for volume overload. Indeed, dialysis patients with a leaner body mass have a higher prevalence of hypertension, poorer hypertension control, and greater left ventricular hypertrophy. Understanding of these body composition changes by aging and sarcopenia can aid clinical decision making in the dry weight assessments in dialysis patients. Advising patients with consistently high interdialytic weight gain to practice salt restriction and providing appropriate nutritional support for malnourished patients with downward trajectory in their dry weight would be of great help to achieve optimal fluid volume status., (© 2018 Wiley Periodicals, Inc.)

The fluid volume balance between intracellular water (ICW) and extracellular water (ECW) gradually changes with age and various medical conditions. Comprehension of these physiological changes would aid in clinical decision-making related to body fluid assessments. A total of 1,992 individuals (753 men and 1,239 women) aged ≥15 yr included in this study had their body composition measurements performed at training gyms in 2014. We developed a regression formula to assess the association of age with the ratio of ECW to ICW in these subjects. The mean ages of male and female subjects were 51.2 ± 15.2 and 57.4 ± 15.2 yr, and their mean body mass indexes were 23.4 ± 3.3 and 21.1 ± 2.8 kg/m 2 , respectively. The total fluid volumes of male and female subjects were 39.6 ± 4.9 and 27.7 ± 3.0 liters, whereas the percent body fat mass per kilogram of body weight were 19 and 26%, respectively. The ECW-to-ICW ratio increased with age because of the steeper decrease in the ICW content than in the ECW content, especially after the age of 70 yr. The regression formulas used for calculating the age-adjusted ECW/ICW ratio were as follows: 0.5857 + 7.4334 × 10 -6  × (age) 2 in men and 0.6062 + 5.5775 × 10 -6  × (age) 2 in women. In conclusion, the fluid imbalance between ICW and ECW contents is driven by decreased cell volume associated with aging and muscle attenuation. Therefore, our proposed formula may serve as a useful assessment tool for the calculation of body fluid composition.

Background: Thallium-201 washout rate of stress myocardial perfusion imaging (MPI) has been reported to correlate with coronary flow reserve which is a parameter of myocardial microcirculation. However, the evidence for its use in diabetic kidney disease (DKD) has been lacking, and the association between thallium-201 washout rate and adverse outcomes including death is unknown. Therefore, the present study was conducted to evaluate the predictive ability of thallium-201 washout rate for mortality in DKD patients initiating hemodialysis., Methods: A total of 96 patients with type 2 diabetes who had been started on maintenance hemodialysis undergoing stress MPI with thallium-201 within 1 year, 72 men and 24 women, with a median age of 67 years, were studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI)., Results: During the mean follow-up period of 3.4 ± 2.1 years, 18 (18.8%) deaths occurred. Cumulative survival rates during the follow-up period, with thallium-201 washout rate levels in the lowest tertile (3.1-36.2%), the middle tertile (36.5-46.3%), and the highest tertile (46.4-66.2%), were 51.0, 86.5, and 85.3%, respectively. Overall, the multivariate Cox regression analysis revealed that thallium-201 washout rate remained an independent predictor of death after adjusting by confounding variables (HR 0.91, 95% CI 0.85-0.97)., Conclusions: Among DKD patients initiating hemodialysis, thallium-201 washout rate seems to be useful for predicting death.

Background: Recent lines of evidence suggest that, as in other countries, sudden cardiac death (SCD) is more common in the Japanese dialysis clinical setting than we previously thought., Summary: Three specific important findings may underlie the increased incidence of SCD in dialysis patients. Even after successful coronary revascularization, hemodialysis (HD) patients continue to have a higher incidence of SCD than the general population. Second, about 70% or more of end-stage kidney disease patients have concentric and eccentric left ventricular hypertrophy, which predisposes many dialysis patients to interstitial fibrosis, decreased coronary perfusion reserve, and decreased ischemia tolerance. Third, mildly impaired left ventricular dysfunction, with an ejection fraction <50%, is associated with a greater risk of SCD in dialysis patients. We have believed and accepted a common sense theory that paroxysmal ventricular tachycardia and fibrillation are the central cause of SCD in HD patients, because such cardiac functional morphological abnormalities were observed, and there are many chances for ventricular arrhythmia triggers, such as volume expansion and electrolyte shift, to develop. However, the type of fatal arrhythmia responsible for SCD differs between before and after HD. Sudden cardiac arrest (SCA) from ventricular fibrillation (VF) was more often seen in the post-HD setting, while SCA from non-VF, which may be bradyarrhythmia, was more often seen in the pre-HD setting. This may imply that the causes of SCA are bradyarrhythmia due to hyperkalemia in the pre-HD setting on the day after a long interval, and fatal ventricular arrhythmia due to a prolonged QT interval in the post-HD setting, because some recent evidence suggests that shifts of electrolytes, such as potassium and calcium, during HD cause rapid prolongation of the QT interval after HD, which may lead to the onset of ventricular arrhythmia and SCD. In fact, a higher calcium gradient, defined as the difference between the pre-HD corrected total serum calcium level and the dialysate calcium level, was associated with a higher risk of SCD in HD patients. Key Messages: Further study is needed to determine which combination of calcium, potassium, and bicarbonate concentrations in dialysate is optimal to avoid SCD in high-risk HD patients., (© 2018 S. Karger AG, Basel.)

We challenged to identify the cutoff value of cTnT in chronic kidney disease (CKD) patients by point of care assessment way. A single center, prospective cross-sectional study was planned and performed. 201 consecutive patients who were visited emergency room for chest symptoms were enrolled in this study. All patients were performed routine practice for differential diagnosis of chest symptom by cardiologist. Simultaneously, semiquantitative measurement of cTnT was performed using same blood sampling on the blind condition to cardiologists for this study. Study patients were divided into four groups according to the estimated glomerular filtration rate (eGFR), CKD1-2, CKD3, CKD4-5, and CKD5D. Usefulness of semiquantitative measurement for diagnosing ACEs was investigated in each group. 77 (38%) of total patient was diagnosed as acute coronary events (ACEs). About 50% of patients were showing cTnT level less than 0.03 ng/mL. The cTnT level over 0.1 ng/mL was found in 30% of total subjects. Mean quantitative value of cTnT was 0.29 ± 0.57 ng/mL in total subjects. Estimated cutoff value in CKD3 patients was 0.088 ng/mL with a sensitivity of 59.3% and specificity of 80.0%. Interestingly, the cutoff values of CKD1-2, CKD4-5, and CKD5D were 0.047, 0.18, and 0.27 respectively, which are half, two times, and three times of CKD3 cutoff value 0.088. The specificities of four cutoff values in each CKD group were showing over 80%, which is higher than sensitivity, respectively. In CKD patients, semiquantitative, point of care assessment of cTnT could be a useful tool for screening for ACEs.

Background: Nausea is a major uremic symptom and a frequent indication for starting dialysis. However, preventive medication for uremic nausea has not yet been identified. Vitamin D receptor activators (VDRAs) may prevent uremic nausea via their pleiotropic actions. The objective of this study was to explore whether VDRA administration during the predialysis period is associated with a reduced prevalence of uremic nausea just prior to beginning dialysis., Methods: A multicenter, retrospective, cross-sectional study was performed to identify a medication to prevent uremic nausea. Patients with stage 5 CKD who were followed-up over 3 months were included. The primary outcomes examined were the prevalence of uremic nausea, congestive heart failure (CHF), and intractable edema at dialysis commencement. The predictor variable was VDRA use during the predialysis period., Results: One thousand five hundred and thirty six patients who had just begun dialysis in nine Japanese facilities between January 2006 and October 2013 were included. Two hundred and thirty (15.0%) patients had commenced dialysis because of uremic nausea, and three hundred and ninety two (25.5%) patients had been using VDRAs before initiating dialysis. Logistic regression analysis showed that, among the medications examined in this study, only VDRA use was independently associated with a lower frequency of uremic nausea (OR 0.512, 95% CI 0.347-0.738, P = 0.0003). On the other hand, CHF and intractable edema were not associated with VDRA administration., Conclusion: Use of VDRAs during the predialysis period was the only factor associated with a lower prevalence of uremic nausea, suggesting that VDRAs may prevent uremic nausea in patients with advanced CKD.

In dialysis patients, electrocardiogram (ECG) abnormalities are common. However, the associations between the T-wave of the lead aVR (aVRT) amplitude and cardiovascular (CV) events or total mortality are unknown. We performed a prospective, observational cohort study of prevalent hemodialysis patients (N = 474), followed for 4 years. Outcomes were composite CV events and all-cause mortality. Predictors were baseline aVRT and other ECG findings. ECG parameters were analyzed in three models: model 1, univariate; model 2, basic adjustments; and model 3, model 2 plus serum albumin, C-reactive protein level, and NT-proBNP. By Cox analysis, aVRT was best associated with both endpoints through model 1 to 3 compared to other ECG findings. Patients categorized according to aVRT amplitude showed a step-by-step increase in hazard ratios for both endpoints. The aVRT amplitude level was significantly associated with not only composite CV events but also with all-cause mortality in prevalent dialysis patients., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease. Most notable is fibroblast growth factor-23 (FGF23), which is thought to be independently associated with cardiac remodeling. Slow progression of cardiac disorders, such as vascular calcification and cardiac remodeling, characterizes cardiac disease due to CKD-MBD. In contrast, fatal arrhythmia may be induced when QT prolongation occurs with CKD-MBD treatment, such as with lower Ca dialysate or the use of calcimimetics. Sudden onset of fatal cardiac events, such as heart failure and sudden cardiac death, due to fatal arrhythmia would be another distinctive phenomenon of CKD-MBD. This may be defined as CKD-MBD-specific cardiac complex syndrome.

Objective: It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA., Design and Method: We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI)., Results: A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level., Conclusion: Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.

Background: Preventive medications for dialysis-requiring congestive heart failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney disease (CKD) are unknown. Our aim was to explore which CKD medication was associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD., Methods: The present multicenter, retrospective, cross-sectional study examined the association between CKD medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD., Results: There were 1536 Japanese Stage 5 CKD patients who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our multivariate analysis, only ARB use was significantly associated with a lower risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516-0.897; p = 0.0064), of the CKD treatments examined in this study., Conclusions: We found that ARB use during the pre-dialysis period is associated with a lower prevalence of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese patients with Stage 5 CKD., (© The Author(s) 2015.)

Although the mechanism of the cardio-renal anaemia syndrome (CRAS) has been elucidated in considerable detail over the past decade, cardiovascular disease (CVD) remains a leading cause of death among patients with end-stage kidney disease (ESKD) undergoing haemodialysis, and these patients' cardiovascular mortality is greater than that of the general population. Recent studies have reported that the CVD risk increases with advancing chronic kidney disease (CKD) stage. Furthermore, the incidence of cardiovascular events is highest during the first week after dialysis initiation, with increased risk in incident haemodialysis patients. This accumulated evidence demonstrates that how patients are managed during the pre-dialysis phase may have important implications on long-term outcomes in ESKD. Anaemia, a non-traditional risk factor for CVD, advances exponentially along with declining kidney function due to insufficient erythropoietin production. Anaemia causes functional abnormalities of the heart, as represented by cardiac hypertrophy, which results from increased cardiac workload induced by an increased preload. Left ventricular hypertrophy (LVH), a traditional risk factor for CVD, is especially associated with advanced CKD stage and could be a major risk factor for cardiovascular complications such as ischaemic heart disease, heart failure, and sudden cardiac death. In ESKD, anaemia develops more severely and requires a higher amount of erythropoiesis-stimulating agent (ESA) therapy before dialysis initiation. This suggests that improvement in anaemia management during the pre-dialysis phase may have a beneficial effect on cardiac hypertrophy and contribute to reducing the CVD risk after initiating haemodialysis., (© 2015 Asian Pacific Society of Nephrology.)

The World Health Organization Fracture Risk Assessment Tool (FRAX(®)) was recently developed to estimate the 10-year absolute risk of osteoporotic fracture among the general population. However, the evidence for its use in chronic kidney disease patients has been lacking, and the association between the FRAX(®) and mortality is unknown. Therefore, a hospital-based, prospective, cohort study was conducted to evaluate the predictive ability of the FRAX(®) for mortality in hemodialysis patients. A total of 252 patients who had been started on maintenance hemodialysis, 171 men and 81 women, with a mean age of 67 ± 14 years, was studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios and 95 % confidence intervals. During the mean follow-up period of 3.4 ± 2.7 years, 61 deaths occurred. The median (interquartile range) of the FRAX(®) for major osteoporotic fracture was 6.9 (4.6-12.0) % in men and 19.0 (7.6-33.0) % in women. Cumulative survival rates at 5 years after starting dialysis, with the FRAX(®) levels above and below the median, were 51.9 and 87.9 %, respectively, in men and 67.4 and 83.7 %, respectively, in women. Overall, in men, the multivariate Cox regression analyses revealed that the log-transformed FRAX(®) remained an independent predictor of death after adjusting by confounding variables. However, in women, the significant association between the FRAX(®) value and the outcome was eliminated if age was put into these models. Among Japanese hemodialysis patients, the FRAX(®) seems to be useful for predicting death, especially in men.

Background/aims: An upright T-wave in lead aVR (aVRT) has recently been reported to be associated with cardiovascular death and mortality among the general population and patients with prior cardiovascular disease (CVD). However, evidence for the predictive ability of aVRT in patients with chronic kidney disease is lacking. Therefore, a hospital-based, prospective, cohort study was conducted to evaluate the predictive ability of an upright aVRT for the short-term prognosis in incident hemodialysis patients., Methods: Among 208 patients who started maintenance hemodialysis, 79 with preexisting CVD (CVD cohort) and 129 with no history of CVD (non-CVD cohort), were studied. An upright and non-upright aVRT were defined as a wave with a positive deflection in amplitude of ≥0 mV and a negative deflection in amplitude of <0 mV, respectively. The endpoint was all-cause death., Results: Overall, the prevalence of an upright aVRT was 22.6% at baseline. During the mean follow-up period of 2.1 ± 1.0 years, 33 deaths occurred. Cumulative survival rates at 3 years after starting dialysis in patients with an upright and non-upright aVRT were 50.0 and 80.7%, respectively, in the CVD cohort and 92.0 and 91.3%, respectively, in the non-CVD cohort. In the CVD cohort, multivariate Cox regression analysis showed that an upright aVRT was an independent predictor of death after adjusting for confounding variables., Conclusion: Among Japanese hemodialysis patients at high risk for CVD, an upright aVRT seems to be useful for predicting death.

Objective: Therapies for chronic kidney disease have changed greatly over the last decade. The aim of this study was to examine the changes in the clinical characteristics and carotid atherosclerosis of patients with end-stage kidney disease (ESKD) over the last 9 years., Methods: A cross-sectional study of 150 consecutive patients with ESKD who had initiated maintenance dialysis between January 2005 and December 2013 was conducted. The patients' mean age was 68 ± 13 years. The group comprised 73% men, and 63% of the patients had diabetic nephropathy. The carotid artery-intima media thicknesses and the plaque scores (PS) were measured using carotid artery ultrasonography within 3 months of dialysis initiation. Changes in the patients' carotid atherosclerosis and clinical characteristics over the years were examined by categorizing the patients into 3 groups representing 3-year intervals based on when dialysis was initiated., Results: The PS declined from 12.8 to 5.4 (P = 0.001). Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol levels declined over the 9-year period (P = 0.005 and P = 0.006, respectively), and the ratio of statin users increased markedly from 24% to 54% (P = 0.001). Univariate regression analysis identified a positive correlation between the PS and LDL-C (r = 0.281; P = 0.01), and a strong positive correlation was found between the PS and LDL-C after adjusting for various risk factors for atherosclerosis., Conclusion: Carotid atherosclerosis in patients with ESKD has decreased over the past 9 years, which may be a consequence of improvements in dyslipidemia management., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Hepatitis B surface antigen is widely used in hepatitis B virus surveillance; patients who test negative for the antigen are judged to be uninfected. However, occult hepatitis B virus infection has been confirmed with hepatitis B virus DNA at low levels in the liver and peripheral blood in patients positive for hepatitis B core antibody or hepatitis B surface antibody, even if they test negative for hepatitis B surface antigen. To investigate the prevalence of occult hepatitis B virus in hemodialysis patients, we performed cross-sectional analysis of 161 hemodialysis patients in two related institutions for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody. Hepatitis B surface antigen, hepatitis B core antibody, or hepatitis B surface antibody was present in 45 patients (28.0%). Hepatitis B virus DNA was present in six patients (3.7%), all of whom also tested positive for hepatitis B core antibody. Hepatitis B surface antibody positivity was unrelated in only one of the six patients. Four of the six patients were positive for hepatitis B surface antigen; however, two (1.3%) of these with occult hepatitis B virus infection were found to be hepatitis B surface antigen negative. Occult hepatitis B virus infection may be missed in hepatitis B virus surveillance using hepatitis B surface antigen alone; therefore, routine hepatitis B core antibody screening is necessary. Patients who test positive for hepatitis B core antibody should undergo further hepatitis B virus DNA testing to enable accurate hepatitis B virus screening., (© 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.)