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Waon therapy is a form of thermal treatment in a dry sauna developed by Tei. Although Waon therapy is reportedly effective for chronic heart failure (CHF) patients, not all patients respond to the therapy. The reason for this ineffectiveness has not been fully clarified. The cardio-ankle vascular index (CAVI) is an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle, and it is thought to reflect some of the afterload of the left ventricle. We investigated the effects of Waon therapy on CAVI and plasma brain natriuretic peptide (BNP) level to clarify the usefulness of CAVI during Waon therapy.CHF patients (n = 21) treated with Waon therapy (2 weeks of 10 sessions) were divided into two groups: responders with an improved BNP level (n = 11) and nonresponders with no improvement in BNP (n = 10). CAVI was measured using Vasela 1500.A significant decrease in CAVI (median and interquartile range) was observed in the responder group (from 10.3 [9.6, 11.6] to 9.6 [8.6, 10.3], P = 0.021), whereas no change was observed in the nonresponder group (from 9.6 [8.6, 10.5] to 9.5 [9.1, 11.2], P = 0.919). The incidence of rehospitalization or cardiac death due to heart failure was significantly higher in patients in whom Waon therapy was ineffective at 12 months of follow-up (log-rank P = 0.001).The effectiveness of Waon therapy in CHF patients may be reflected by the improvement in CAVI.

Background Etelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan. Methods This PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician’s discretion. Results Of 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60–240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled. Conclusion This was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

Aim Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs. Methods We performed post hoc analyses of a 52‐week, open‐label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses. Results There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60‐240 pg/mL, 8.4‐10.0 mg/dL and 3.5‐6.0 mg/dL, respectively) across the three groups. TRACP‐5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group. Conclusion The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment., SUMMARY AT A GLANCE This is a small observational study of the effect of dialysate calcium concentrations on etelcalcetide with concomitant drugs in secondary hyperparathyroidism. No statistically significant differences were found between the different dialysate calcium groups suggesting that calcium concentrations in the dialysate do not modulate the effect of etelcalcetide.

Ferric citrate hydrate (FC) is an iron-based phosphate binder approved for hyperphosphataemia in patients with chronic kidney disease. We conducted a randomised controlled trial to evaluate the effects of FC on anaemia management in haemodialysis patients with hyperphosphataemia. We 1:1 randomised 93 patients who were undergoing haemodialysis and being treated with non-iron-based phosphate binders and erythropoiesis-stimulating agents (ESA) to receive 24 weeks of FC or to continue their non-iron-based phosphate binders (control) in a multicentre, open-label, parallel-design. Phosphate level was controlled within target range (3.5–6.0 mg/dL). The primary endpoint was change in ESA dose from baseline to end of treatment. Secondary endpoints were changes in red blood cell, iron and mineral, and bone-related parameters. Compared with control, FC reduced ESA dose [mean change (SD), −1211.8 (3609.5) versus +1195 (6662.8) IU/week; P = 0.03] without significant differences in haemoglobin. FC decreased red blood cell distribution width (RDW) compared with control. While there were no changes in serum phosphate, FC reduced C-terminal fibroblast growth factor (FGF) 23 compared with control. The incidence of adverse events did not differ significantly between groups. Despite unchanged phosphate and haemoglobin levels, FC reduced ESA dose, RDW, and C-terminal FGF23 compared with control.

Background Calcium carbonate is a first-line therapy for hyperphosphatemia in hemodialysis patients but is associated with progressive coronary and aortic calcification. Sevelamer compounds are alternatives to calcium-containing phosphate binders as they contain lower calcium levels. The sevelamer compound, bixalomer, is a calcium-free insoluble polymer that has been shown to be effective and safe in comparison with calcium carbonate. We therefore compared the effect of bixalomer vs calcium carbonate on coronary artery calcification in hemodialysis patients with hyperphosphatemia. Methods In this open-label, randomized phase IV trial across 23 sites throughout Japan, 85 patients with chronic kidney disease were randomized to bixalomer (n = 44) or calcium carbonate (n = 41) therapy and monitored for 12 months. Bixalomer was administered at a dosage of 1500 mg/day (500 mg three times a day) and calcium carbonate was administered at a dosage of 3000 mg/day (1000 mg three times a day). The primary outcome was the change in coronary artery calcium over time measured using computed tomography. Levels of serum phosphorus, calcium, intact parathyroid hormone, and the occurrence of adverse events were also reported over the course of the study. Results The mean (± standard deviation) changes in coronary artery calcium scores from baseline to 12 months were significantly higher in the calcium carbonate vs bixalomer group (268.6 ± 320.1 vs 126.7 ± 154.8, respectively; between-group difference p = 0.029). At 12 months in the bixalomer group, serum phosphorus and intact parathyroid hormone levels were significantly higher; serum calcium was significantly lower (p

Purpose Secondary hyperparathyroidism (SHPT) is a serious complication that increases the risk of bone disorders in patients with chronic kidney disease (CKD) undergoing hemodialysis. Etelcalcetide is the first injectable calcimimetic approved for treatment of SHPT, which reduces bone turnover markers and suppresses intact fibroblast growth factor 23 (iFGF-23). This study aimed to explore the associations between etelcalcetide-induced changes in circulating factors and serum iFGF-23 levels. Methods This study was a post hoc analysis of data from a previous multicenter, open-label study of etelcalcetide administered to 191 Japanese patients with SHPT undergoing hemodialysis for 52 weeks. Correlations were analyzed between changes from baseline in serum iFGF-23 and serum intact parathyroid hormone (iPTH), corrected calcium, phosphate, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRACP-5b), and 1α,25-dihydroxyvitamin D (1,25[OH]2D) levels at 1, 2, 3, 6, and 12 months. Akaike's Information Criterion (AIC) was calculated using serum iPTH, corrected calcium, phosphate, BAP, TRACP-5b, and 1,25(OH)2D levels as potential predictor variables at each time point. Four models with the smallest AIC at the 3-month time point were chosen as the fitted models to predict changes in iFGF-23 levels, and stepwise multivariate analysis was performed to determine the predictor variables with the greatest contribution to the change in iFGF-23 levels by calculating the partial coefficients of determination. Findings The etelcalcetide-induced reduction in iFGF-23 was positively correlated with serum levels of corrected calcium and phosphate and negatively with BAP. By calculating the AIC, corrected calcium, phosphate, iPTH, BAP, and TRACP-5b were suggested to be predictors of iFGF-23 levels. Stepwise multivariate analysis found that phosphate, corrected calcium, BAP, and TRACP-5b correlated with iFGF-23, in order from strongest to weakest. Implications These results suggest that etelcalcetide effectively lowered iFGF-23 and that this reduction may occur via improvements in phosphate, corrected calcium, BAP, and TRACP-5b. Etelcalcetide is thus a promising calcimimetic for decreasing iFGF-23 and improving bone turnover in patients with CKD undergoing hemodialysis with severe SHPT, in addition to decreasing PTH itself. JapicCTI identifier: 142,665.

Objective Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities in fatty acid and organic acid metabolism; however, the details are unknown. We investigated the association between carnitine profiles before and after dialysis and the erythropoiesis-stimulating agent (ESA) resistance index (ERI), which is a significant prognostic factor in patients on maintenance hemodialysis. Design and Methods cross-sectional study. We measured the carnitine profile of 79 patients on maintenance hemodialysis before and after dialysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the ERI and pre-dialysis carnitine profile, removal rate of various carnitines, and previously-reported ERI-related factors were investigated. Significant factors were determined with stepwise multiple regression analysis and validated with the bootstrap method. SPSS version 22.0 was used for analysis, and P

Background The inferior vena cava (IVC) dimensions represent the right ventricular preload, whereas the peak early mitral inflow wave velocity (peak E-velocity) represents the left ventricular preload. On the other hand, B-lines represent extravascular lung water. The aim of this study was to evaluate possible acute changes in the IVC dimensions, peak E-velocity, and number of B-lines during hemodialysis therapy. Methods A total of 55 consecutive patients receiving maintenance hemodialysis were enrolled in this study. We performed echo-graphic examinations at three time points (just after the start, during the middle, and just before the end of the hemodialysis therapy). We then investigated the changes in the IVC dimensions, peak E-velocity, and number of B-lines. Results The peak E-velocity decreased from 80 ± 26 cm/s at the start of the therapy to 58 ± 22 cm/s during the middle and 51 ± 21 cm/s at the end of the therapy. The IVC dimensions also decreased from 15 ± 4 mm at the start of the therapy to 12 ± 3 mm during the middle and 11 ± 3 mm at the end of the therapy. The number of B-lines also decreased from 12 ± 5 at the start of the therapy to 9 ± 4 during the middle and 5 ± 3 at the end of the therapy. The changes in the peak E-velocity and IVC dimensions were significantly greater during the first half of the dialysis period than during the second half of the dialysis period (P

The dialysis practice guideline in Japan sets a limit on the allowed interdialytic weight gain (IDWG)6%. However, the effects of relative gain of fluid volume to body weight may differ in presence of morbid conditions. Here, we examined whether or not the associations between IDWG and mortality differ by serum albumin (sAlb), a nutritional and illness marker.The study type used was prospective cohort study.Patients who participated in the Japan Dialysis Outcomes and Practice Pattern Study (phase 1-4 [1999-2011]) and received thrice-weekly hemodialysis.IDWG was the exposure of interest and was collected every 4 months, divided into 7 categories as follows:2%, 2% to 3%, 3% to 4% (reference), 4% to 5%, 5% to 6%, 6% to 7%, and7%. sAlb was treated as both an effect modifier and confounder and dichotomized into ≥3.8 g/dL and3.8 g/dL segments, according to the protein-energy wasting criteria proposed by the International Society of Renal Nutrition and Metabolism.The outcome in this study was all-cause mortality.A total of 8,661 patients were analyzed. Time-varying Cox regression analyses revealed that, when sAlb was ≥3.8 g/dL, an IDWG7% was associated with greater risk of mortality (adjusted hazard ratio [AHR] 2.74; 95% confidence interval [CI], 1.49-5.05). When sAlb was3.8 g/dL, however, IDWGs2% (AHR 1.89; 95% CI, 1.50-2.39) and 4% to 5% (AHR 0.75; 95% CI, 0.58-0.96) were associated with mortality (P for interaction = .001). Cubic spline analyses showed that the mortality increased when IDWG exceeded 6% for patients with sAlb ≥3.8 g/dL; in contrast, for patients with sAlb3.8 g/dL, the mortality increased when IDWG was3% and decreased when IDWG was between 4% and 6%.The main limitation was possible residual confounding.The direction and magnitude of the associations between IDWG and mortality were modified by sAlb. Dialysis experts should take these results into account when revising the clinical practice guidelines.

Introduction A recent study suggested that orally dosed ferric citrate hydrate (FC) corrects renal anemia in patients on hemodialysis (HD), suggesting biological differences in effects of iron supplementation using different routes of administration. To address this issue, the present study compared oral FC with i.v. saccharated ferric oxide (FO) in stable HD patients. Methods Participants comprised 6 patients administered 3 consecutive protocols in the first HD session of the week in a fasting state: nothing given, as control (C); oral load of FC (480 mg iron), and 5 minutes of i.v. FO (40 mg iron). Iron dynamics in the body and biological impact on redox-inflammation status during the study (6 hours) were examined. Results Significant increases in serum iron and transferrin saturation were seen with both FC and FO. Regarding total iron-binding capacity as the sum of serum iron and unsaturated iron-binding capacity, no changes were found in FC, whereas significant increases were seen in FO (appearance of non–transferrin-binding iron [NTBI]), despite the lower serum iron levels in FO. Compared with C, increases were seen in serum myeloperoxidase (oxidative marker) with accompanying significant decreases in thioredoxin (antioxidant) in FO, whereas no changes were found in FC. Conclusion Oral FC differs from i.v. FO in areas such as less NTBI generation and less induction of oxidative stress. The result indicates potential clinical benefits of oral FC in terms of iron supplementation for renal anemia in HD patients.

Introduction The pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism. Methods This multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisted of a single dose part and a multiple dose (3 times weekly for 4 weeks) part. Major inclusion criteria were hemodialysis for at least 90 days, serum intact parathyroid hormone (iPTH) ≥ 300 pg/ml, and serum albumin-corrected Ca (cCa) ≥ 9.0 mg/dl. There were 3 single-dose cohorts (n = 6 each) randomized 2:1 to 5, 10, or 20 mg etelcalcetide or placebo, and 2 multiple-dose cohorts (n = 11 each) randomized 8:3 to 2.5 or 5 mg etelcalcetide or placebo. Results Etelcalcetide plasma concentration decreased rapidly after i.v. administration, generally remained stable from 24 hours postdose to the next dialysis, and then decreased by dialysis. Etelcalcetide exposure increased dose proportionally. Etelcalcetide plasma predialysis concentration reached almost steady state at week 4. A single dose of etelcalcetide dose-dependently reduced serum iPTH in 30 minutes, and the reduction reached a plateau at 1 hour that lasted until 8 hours. The percent change from baseline serum iPTH thereafter showed a trend to gradually decrease; it was still −30% or greater on day 3. Similar results were obtained at the last injection (days 27–29) of the multiple dose. The effect of the multiple dose was sustained during the interdialytic period. Etelcalcetide decreased serum cCa in a more gradual but dose-dependent and sustained manner. Discussion Etelcalcetide dose-dependently reduced serum iPTH and serum cCa. Moreover, the effect was sustained in the interdialytic period.

Introduction In hemodialysis patients on ferric citrate hydrate, the increase in ferritin level is mainly due to the administration of the compound. We investigated possible other factors associated with ferritin level and how erythropoietin resistance index and erythropoiesis in those patients were affected. We looked at ferritin-elevating factors using data from a Japanese phase III long-term clinical trial of ferric citrate hydrate. Methods The factors with a strong association with ferritin levels at week 28 were selected by the process of variable selection. In addition, selected factors were analyzed by Mixed Model for Repeated Measurement. Subjects were divided into 3 groups by quantiles (

Background In recent years, the use of chest ultrasonography to detect lung water has received growing attention in clinical research. Estimation of the number of B-lines using lung ultrasound is now a standard method for the evaluation of pulmonary congestion. In the present study, we examined the relation between the number of B-lines and clinical parameters in hemodialysis patients. Methods A total of 49 consecutive patients receiving maintenance hemodialysis were enrolled in this study. Lung ultrasound was performed using Vscan® (GE Healthcare, Japan). Bilateral scanning of the anterior and lateral chest walls was performed with the patient in a supine position just after the start of the hemodialysis therapy. The total number of B-lines was estimated. We investigated the relationships between the number of B-lines and other clinical parameters. Results Patient heart rate and the serum log [NT-proBNP] level were positively correlated (P = 0.009 and 0.003, respectively), and body weight and the serum albumin and creatinine level were negatively correlated with the number of B-lines (P = 0.023, 0.001, and 0.011, respectively). Conclusions The number of B-lines was positively correlated with the serum N-terminal pro-brain natriuretic peptide level. Lung ultrasound can quantify lung edema. Body weight and the serum albumin and creatinine level were negatively correlated with the number of B-lines. Careful attention to the presence of pulmonary edema is needed in patients with a low body weight and a low serum albumin and creatinine level.

We found that community-dwelling women with 25-hydroxyvitamin D levels

Serum ferritin level and transferrin saturation (TSAT) are widely used to evaluate iron status in patients with chronic kidney disease, and are also important variables for performing statistical analyses. Many guidelines have set control targets or upper limits for these markers. Inter-method variability is an important consideration in iron control and statistical analysis. We used 10 ferritin assay kits and five iron/unsaturated iron-binding capacity/total iron-binding capacity assay kits to determine ferritin levels and TSAT in 114 patients on maintenance dialysis, and evaluated measurement bias using Passing-Bablok regression analyses. The variance of distributions categorized by differences in assay kits was examined using Fisher's exact test. Slopes ranged from 1.00 to 1.63 (1.00 to 0.61) for ferritin and 1.00 to 1.10 (1.00 to 0.91) for TSAT. The distribution according to the 2015 JSDT Guideline for Renal Anemia in Chronic Kidney Disease significantly changed (P = 0.01). TSAT thus provides more precise control than ferritin in multi-center comparisons where no particular assay is specified. Developers must reduce variability in serum ferritin assay kits. Researchers must analyze measured values by taking into account the propagation of errors, and clinicians must evaluate laboratory data carefully.

Progression of anemia in patients with chronic kidney disease (CKD) is associated with an increased risk of death and hospitalization. It is not sufficiently clear whether treating renal anemia with recombinant human erythropoietin (rHuEPO) has a beneficial effect on early survival after hemodialysis (HD) initiation in patients with CKD. The study was an open-label multicenter retrospective cohort study to evaluate the relationship between rHuEPO treatment and early survival after HD initiation in patients with CKD. Predialysis patients with CKD were divided into two groups: an rHuEPO-treated group (rHuEPO group) and a non-treatment group. The primary endpoint was all-cause mortality in the year after HD initiation. A total of 3261 patients were enrolled (2275 in the rHuEPO group and 986 in the non-treatment group). One-year survival was 95.36% in the rHuEPO group and 90.36% in the non-treatment group. The survival rate was significantly higher in the rHuEPO group (P < 0.0001). The results of multivariate analysis confirmed that predialysis treatment with rHuEPO is a predictor for reduced mortality risk (hazard ratio = 0.61, 95% confidence interval: 0.42-0.87, P = 0.006). Risk for the composite event of death/hospitalization was also lower in the rHuEPO group (hazard ratio = 0.88, 95% confidence interval: 0.78-0.98, P = 0.026). The results of this study suggest that treatment with rHuEPO can decrease early mortality risk after initiation of HD in patients with CKD. A prospective study is needed to further investigate early survival after HD initiation.

Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient-years. Atrial fibrillation was independently associated with all-cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15-1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55-1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected.

IntroductionThe relationship between intradialytic ultrafiltration volume and vascular access (VA) patency remains unclear. Using data from the Japan Dialysis Outcomes and Practice Patterns Study, we analyzed whether large-volume ultrafiltration was associated with VA failure in hemodialysis patients.MethodsWe included 2736 patients for whom it was possible to evaluate VA patency and bodyweight change during dialysis. Patients were divided into three groups according to the tertile of intradialytic ultrafiltration by bodyweight: low, -9.5%-3.8%; middle, 3.8%-5.1%; and high, 5.1%-13.7%. Primary VA patency was defined as the time to first VA intervention, and secondary patency as the time to creation of a new VA. Hazard ratios for VA failure were compared across groups by using Cox regression models adjusted for age, sex, body mass index, diabetes, hemoglobin and phosphorus levels, Kt/V, and erythropoiesis-stimulating agent and antiplatelet use.ResultsFor the low, middle, and high groups, the incidences of primary and secondary VA patency were 4.7, 5.6, and 6.7 events/100 person-years and 1.3, 1.6, and 1.7 events/100 person-years, respectively. Adjusted hazard ratios for primary VA patency in the middle and high groups versus the low group were 1.16 (95% confidence interval [CI], 0.88-1.52) and 1.41 (95% CI, 1.07-1.87), respectively; those for secondary VA patency were 1.29 (95% CI, 0.78-2.13) and 1.45 (95% CI, 0.86-2.45), respectively.DiscussionLarge-volume ultrafiltration during dialysis tended to increase VA failure in hemodialysis patients. We thus recommend smaller ultrafiltration volumes during hemodialysis to secure VA safely.

To help relieve the burden of dietary restrictions experienced by many hemodialysis (HD) patients, dialysis staff may encourage patients, with no consideration to the degree of family support. Here, we clarified the effect of staff encouragement and living conditions on the burden of dietary restrictions in HD patients. This retrospective cohort study was conducted using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) I and III. We enrolled patients aged 18-75 years on HD therapy for at least 3 months. We categorized patients into four groups based on combinations of level of staff encouragement (high or low) and living condition (alone or with family) at baseline survey. Patients who felt they received high staff encouragement and lived with their family were set as the control. The main outcome was increase in patients' perceived burden of dietary restriction after 1 year. 1377 (69.1%) felt they received high staff encouragement, and 176 (9.1%) were living alone. After 1 year, 537 (26.9%) patients reported feeling an increased burden of dietary restriction. A low level of staff encouragement did not increase the burden in any patients, regardless of living situation. However, a high level of staff encouragement did increase the burden in patients living alone (adjusted odds ratio: 1.57, 95% confidence interval: 1.05-2.36). We observed an unexpected association between high staff encouragement and increased burden of dietary restriction among patients living alone. Staff encouragement may not relieve patients' burden with respect to dietary restriction and may in fact exacerbate it.

Background Limited attention has been paid to the relationship between bladder dysfunction and motor disorder in multiple system atrophy (MSA). Objective We aimed to correlate pressure-flow urodynamic parameters with video-gait analysis parameters in MSA. Methods We recruited 34 patients with MSA: 20 men, 14 women; age 64.0 + − 7.9 years; disease duration 2 years (1–4 years). Nineteen cases had the cerebellar form, and 15 had the parkinsonian form; the patients were taking levodopa 300 mg/day (100–400 mg). All patients underwent pressure-flow urodynamics (parameters: detrusor overactivity [noted in 72%] and Watts factor) and video-gait analysis (parameters: time and the number of strides taken to walk 5 m (simple task) and time for timed up and go (complex task). Statistical analysis was done using Student's t-test to analyze the relation between detrusor overactivity and gait, and Spearman's rank correlation coefficient test to analyze the relation between the remaining parameters and gait. Results We found no relation between filling-phase urodynamics (detrusor overactivity) and video-gait analysis parameters. Also, we found no relation between voiding-phase urodynamics (Watts factor, reflecting detrusor power) and all three video-gait analysis parameters in our MSA patients. Conclusion The fact that neither detrusor overactivity nor the Watts factor was related with motor disorders in the present study suggests that bladder dysfunction occurs independently from motor disorder in MSA.

A fatal mix-up of a hemofilter with a plasma separator occurred in 2011. The close resemblance between the two blood purification columns commonly used in Japan posed a fundamental risk for such mix-ups. Both the in-hospital case investigation committee and the relevant academic societies have independently proposed the modifications of the dialysate port (D port) of the plasma separator to avoid this type of misuse. To make these devices foolproof, medical professionals, including physicians and clinical engineers, and members of the Medical Technology Association of Japan discussed measures to prevent this type of recurrence. Since new standards were soon to be issued by the International Organization for Standardization (ISO), the modifications were temporarily postponed. In September 2016, the ISO released new standards for small-bore connectors. The shape changes of the D port from the current slip-in type (ISO8637) to the Luer lock type (ISO80369-7) had been already approved by the Ministry of Health, Labor and Welfare of Japan by the end of November 2018, including a temporal use of a converter to connect the current type of D port to the new type of blood circuit. We must address the next issue that the new standard and the older standard coexist in the clinical setting, which may create a new risk.

In this study including the field of metabolomics approach for food, the evaluation of untargeted compounds using HILIC-ESI/TOF/MS and multivariate statistical analysis method is proposed for the assessment of classification, contamination and degradation of infant formula. HILIC mode is used to monitor more detected numbers in infant formulas in the ESI-positive scan mode than the reversed phase. The repeatability of the non-targeted contents from 4 kinds of infant formulas based on PCA was less than the relative standard deviation of 15% in all groups. The PCA pattern showed that significant differences in the classification of types and origins, the contamination of melamine and the degradations for one week were evaluated using HILIC-ESI/TOF/MS. In the S-plot from the degradation test, we could identify two markers by comparison to standards as nicotinic acid and nicotinamide. With this strategy, the differences from the untargeted compounds could be utilized for quality and safety assessment of infant formula.

ABH-F and ABH-P have been developed for hemodiafiltration (HDF) therapy. In this study, we evaluated the solute removal characteristics of the hemodiafilters in a bovine blood in vitro study. The hemodiafilters were examined for 120 min at various filtration flow rates (Q F) (31.2–250 mL/min) under a constant blood flow rate of 250 mL/min and constant dialysate flow rates of 500/250 mL/min in pre-dilution HDF (pre-HDF) and post-dilution HDF (post-HDF). Creatinine clearance in pre-HDF was approximately 85 % of that in post-HDF because it was removed by molecular diffusion dominantly. The initial clearances of β2-microglobulin and α1-microglobulin increased with Q F and these values slightly and steeply decreased with time due to membrane fouling. Under a same Q F of 62.5 mL/min, higher clearance values in post-HDF were obtained compared with those in pre-HDF. All clearance values of ABH-P were higher than those of ABH-F under the same Q F. It seems that the ABH-P has a larger pore size of membrane than that in ABH-F. The creatinine and α1-microglobulin clearance values were obtained as highest at post-Q F62.5, the β2-microglobulin clearance values and transmembrane pressure were obtained as highest at pre-Q F250. Large solute clearances such as α1-microglobulin and albumin decreased with time in all HDF experiments. Time decay of large solute clearance values was observed in the HDF modality that had a higher clearance of the solute at 5 min later after the start of experiment.

Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients. Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction. This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat (10 mg daily) group and a control group and measured flow-mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood pressure, malondialdehyde-modified low-density lipoprotein (MDA-LDL), and highly sensitive C-reactive protein (hsCRP) at baseline and at the end of a 4-week study period. Flow-mediated dilation increased from 5.3% ± 2.4% to 8.9% ± 3.6% in the febuxostat group but did not change significantly in the control group. Treatment with febuxostat resulted in a significant decrease in serum UA level and a significant decrease in MDA-LDL compared with baseline, but no significant difference was observed in hsCRP level or blood pressure. No significant differences were observed in the control group. Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia.

Because of multiple comorbidities, hemodialysis (HD) patients are prescribed many oral medications, including phosphate binders (PBs), often resulting in a high “pill burden.” Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we assessed associations between PB pill burden, patient-reported PB non-adherence, and levels of serum phosphorus (SPhos) and parathyroid hormone (PTH) using standard regression analyses. The study included data collected from 5262 HD patients from dialysis units participating in the DOPPS in 12 countries. PB prescription ranged from a mean of 7.4 pills per day in the United States to 3.9 pills per day in France. About half of the patients were prescribed at least 6 PB pills per day, and 13% were prescribed at least 12 PB pills per day. Overall, the proportion of patients who reported skipping PBs at least once in the past month was 45% overall, ranging from 33% in Belgium to 57% in the United States. There was a trend toward greater PB non-adherence and a higher number of prescribed PB pills per day. Non-adherence to PB prescription was associated with high SPhos (>5.5 mg/dL) and PTH (>600 pg/mL). Adherence to PB is a challenge for many HD patients and may be related to the number of PB pills prescribed. Prescription of a simplified PB regimen could improve patient adherence and perhaps improve SPhos and PTH levels.

Yuzo Watanabe, Kunihiro Yamagata, Shinichi Nishi, Hideki Hirakata, Norio Hanafusa, Chie Saito, Motoshi Hattori, Noritomo Itami, Yasuhiro Komatsu, Yoshindo Kawaguchi, Kazuhiko Tsuruya, Yoshiharu Tsubakihara, Kazuyuki Suzuki, Ken Sakai, Hideki Kawanishi, Daijo Inaguma, Hiroyasu Yamamoto, Yoshiaki Takemoto, Noriko Mori, Kazuyoshi Okada, Hiroshi Hataya, Takashi Akiba, Kunitoshi Iseki, Tadashi Tomo, Ikuto Masakane, Tadao Akizawa, and Jun Minakuchi, for “Hemodialysis Initiation for Maintenance Hemodialysis” Guideline Working Group, Japanese Society for Dialysis Therapy

Yuzo Watanabe, Hideki Kawanishi, Kazuyuki Suzuki, Shigeru Nakai, Kenji Tsuchida, Kaoru Tabei, Takashi Akiba, Ikuto Masakane, Yoshiaki Takemoto, Tadashi Tomo, Noritomo Itami, Yasuhiro Komatsu, Motoshi Hattori, Michio Mineshima, Akihiro Yamashita, Akira Saito, Hidemune Naito, Hideki Hirakata, and Jun Minakuchi, for “Maintenance Hemodialysis: Hemodialysis Prescriptions” Guideline Working Group, Japanese Society for Dialysis Therapy

Objective Atherosclerosis, which causes cardiovascular disease, is a major cause of death in hemodialysis (HD) patients. Eicosapentaenoic acid (EPA), an anti-hyperlipidemic agent, is known to have antioxidative or anti-inflammatory effects, resulting in improvements in atherosclerosis. In the present study, we examined whether EPA improves the all-cause mortality in patients receiving regular HD therapy. Methods We enrolled 176 patients treated with maintenance HD therapy and performed a longitudinal observational cohort study for three years. We divided the patients into two groups based on whether or not the received EPA treatment [EPA(+) and EPA(-), respectively]. The primary end-point was all-cause death. We also matched the two groups using propensity score matching and examined the effect of EPA. Results Before matching, the all-cause mortality rates were 24.0% in the EPA(+) and 11.8% in the EPA(-) groups, which were significantly different (p=0.044). After propensity score matching, the EPA(+) group still showed a significantly better prognosis than the EPA(-) group (p=0.038). A multivariate analysis showed that EPA treatment significantly reduced the risk of all-cause mortality both before and after propensity score matching. Conclusion EPA treatment is independently associated with lower mortality in HD patients.

Background/Aims: JTT-751 (ferric citrate hydrate) is a novel iron-based phosphate approved in Japan for the treatment of hyperphosphatemia in dialysis and nondialysis patients with chronic kidney disease. Methods: In this phase 3, multicenter, open-label, dose-adjusted study, we investigated the efficacy and safety of JTT-751 in peritoneal dialysis patients. A total of 56 patients with serum phosphate ≥5.6 and Results: Serum phosphate was significantly reduced by 2.26 mg/dl (p < 0.001). The percentage of patients achieving target serum phosphate levels was 76.8%. Intact parathyroid hormone decreased significantly (p < 0.001). The most common adverse drug reactions were diarrhea and constipation. Most of the events were considered to be mild. Treatment with JTT-751 resulted in significant increases in serum ferritin and transferrin saturation (p < 0.001). Conclusion: In peritoneal dialysis patients with hyperphosphatemia, 12-week treatment with JTT-751 resulted in significant reductions in serum phosphate while simultaneously increasing serum iron parameters. JTT-751 was well tolerated.

Secondary hyperparathyroidism (SHPT) is one of the major complications of chronic kidney disease (CKD) and is associated with elevated serum intact parathyroid hormone (iPTH). Calcitriol, a non-selective vitamin D receptor agonist (VDRA) that suppresses iPTH is used for SHPT treatment, but its use is frequently complicated by hypercalcemia. Paricalcitol, a selective VDRA, demonstrated efficacy in iPTH suppression compared to maxacalcitol in a Phase 2 study (M11-609) in Japanese subjects. The current larger Phase 3 study (M11-517), evaluated the efficacy of intravenous paricalcitol injection compared to intravenous maxacalcitol injection with respect to iPTH and calcium control using a non-inferiority primary endpoint. In this double-blind, double-dummy, parallel-group study, eligible Japanese CKD subjects with SHPT on hemodialysis were randomized 1:1 to receive intravenous paricalcitol or intravenous maxacalcitol injections for 12 weeks. Dynamic allocation of subjects on the basis of screening iPTH levels was used to ensure equal distribution of subjects with iPTH

Missed hemodialysis (HD) treatments not due to hospitalization have been associated with poor clinical outcomes and related in part to treatment nonadherence. Using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012-2015), we report findings from an international investigation of missed treatments among patients prescribed thrice-weekly HD.Prospective observational study.8,501 patients participating in DOPPS, on HD therapy for more than 120 days, from 20 countries. Longitudinal and cross-sectional analyses were performed based on the 4,493 patients from countries in which 4-month missed treatment risk was5%.The main predictor of patient outcomes was 1 or more missed treatments in the 4 months before DOPPS phase 5 enrollment; predictors of missed treatments included country, patient characteristics, and clinical factors.Mortality, hospitalization, laboratory measures, patient-reported outcomes, and 4-month missed treatment risk.Outcomes were assessed using Cox proportional hazards, logistic, and linear regression, adjusting for case-mix and country.The 4-month missed treatment risk varied more than 50-fold across all 20 DOPPS countries, ranging from 1% in Italy and Japan to 24% in the United States. Missed treatments were more likely with younger age, less time on dialysis therapy, shorter HD treatment time, lower Kt/V, longer travel time to HD centers, and more symptoms of depression. Missed treatments were positively associated with all-cause mortality (HR, 1.68; 95% CI, 1.37-2.05), cardiovascular mortality, sudden death/cardiac arrest, hospitalization, serum phosphorus level 5.5mg/dL, parathyroid hormone level 300pg/mL, hemoglobin level 10g/dL, higher kidney disease burden, and worse general and mental health.Possible residual confounding; temporal ambiguity in the cross-sectional analyses.In the countries with a 4-month missed treatment risk5%, HD patients were more likely to die, be hospitalized, and have poorer patient-reported outcomes and laboratory measures when 1 or more missed treatments occurred in a 4-month period. The large variation in missed treatments across 20 nations suggests that their occurrence is potentially modifiable, especially in the United States and other countries in which missed treatment risk is high.

Secondary hyperparathyroidism (SHPT) is a serious major complication in hemodialysis patients with chronic kidney disease. Long-term maintenance of serum phosphate, calcium, and parathyroid hormone (PTH) levels in appropriate ranges in these patients is a major challenge. We investigated the efficacy and safety of long-term treatment with etelcalcetide, a novel intravenous calcimimetic, in Japanese SHPT patients on long-term hemodialysis. This study was a multicenter open-label study. A total of 191 hemodialysis patients with serum intact PTH (iPTH) > 240 pg/mL were enrolled. Etelcalcetide was administered thrice weekly for 52 weeks, with an initial dose of 5 mg and flexibility to adjust the dose between 2.5 and 15 mg and to adjust the dosing of concomitant medications for SHPT. The efficacy endpoint was the proportion of patients with serum iPTH decreased to the target range (60–240 pg/mL). Serum iPTH levels decreased immediately after etelcalcetide was started. At the end of the study, 87.5% (95% confidence interval 81.4–92.2; 140/160 patients) of patients achieved target serum iPTH levels, with control of serum calcium and phosphate levels. Adverse events, mostly mild to moderate, were reported by 96.8% of patients and led to study discontinuation in 7.4% of patients. Nausea, vomiting, and symptomatic hypocalcemia were found in 4.7, 9.5, and 1.1%, with 0.5, 1.1, and 1.1% considered treatment-related. Etelcalcetide effectively maintained serum iPTH, calcium, and phosphate levels in appropriate ranges with concomitant medications for SHPT for 52 weeks in Japanese hemodialysis patients, and was safe and well tolerated. JapicCTI-142665.

Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities in fatty acid and organic acid metabolism; however, the details are unknown. We investigated the association between carnitine profiles before and after dialysis and the erythropoiesis-stimulating agent (ESA) resistance index (ERI), which is a significant prognostic factor in patients on maintenance haemodialysis.This was a cross-sectional study. We measured the carnitine profile of 79 patients on maintenance haemodialysis before and after dialysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the ERI and pre-dialysis carnitine profile, removal rate of various carnitines, and previously-reported ERI-related factors were investigated. Significant factors were determined with stepwise multiple regression analysis and validated with the bootstrap method. SPSS version 22.0 was used for analysis, and P0.05 was considered statistically significant.The removal rate of long-chain acylcarnitine with dialysis was lower than that of short-chain or medium-chain acylcarnitines. Stepwise multiple regression analysis (n = 79) demonstrated that 3-hydroxy isovalerylcarnitine (C5-OH, P0.001, β = -0.469) and stearoylcarnitine (C18, P0.001, β = 0.390) were independent significant factors (RERI positively correlated with long-chain C18 acylcarnitine and negatively correlated with short-chain C5-OH acylcarnitine. C5-OH and C18 acylcarnitines at baseline might be contributing factors in distinguishing responders from nonresponders after L-carnitine administration.