Cardio-Ankle Vascular Index Reflects the Efficacy of Waon Therapy in Heart Failure Patients.

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.

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan.

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.

Influence of dialysate Ca concentrations on the therapeutic effects of etelcalcetide with concomitant drugs in patients with secondary hyperparathyroidism.

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.

Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients.

Hepatitis C virus (HCV) infection is common in dialysis patients and is associated with increased morbidity and mortality. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS, 1996-2015) to assess trends in the prevalence, incidence, and risk factors for HCV infection as defined by a documented diagnosis or antibody positivity. Among prevalent hemodialysis patients, HCV prevalence was nearly 10% in 2012-2015. Prevalence ranged from 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. HCV prevalence decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had recently (<4 months) initiated dialysis. The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced 3 or more cases over a median of 1.1 years. High HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates. Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population. Combined with a high prevalence of HCV infection among patients with Stage 5 CKD, high rates of HCV seroconversion in a subset of hemodialysis units may contribute to this disparity.

Missed Hemodialysis Treatments: International Variation, Predictors, and Outcomes in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 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 was > 5%. PREDICTORS: 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. OUTCOMES: Mortality, hospitalization, laboratory measures, patient-reported outcomes, and 4-month missed treatment risk. ANALYTICAL APPROACH: Outcomes were assessed using Cox proportional hazards, logistic, and linear regression, adjusting for case-mix and country. RESULTS: 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. LIMITATIONS: Possible residual confounding; temporal ambiguity in the cross-sectional analyses. CONCLUSIONS: In the countries with a 4-month missed treatment risk > 5%, 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.

Long-term effects of etelcalcetide as intravenous calcimimetic therapy in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. REGISTRATION NUMBER: JapicCTI-142665.

Association between resistance to erythropoiesis-stimulating agents and carnitine profile in patients on maintenance haemodialysis.

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 haemodialysis. METHODS: 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 P < 0.05 was considered statistically significant. RESULTS: 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, P < 0.001, ß = -0.469) and stearoylcarnitine (C18, P < 0.001, ß = 0.390) were independent significant factors (R2 = 0.239) of ERI. The bootstrap method similarly indicated these two to be significant factors. CONCLUSION: ERI 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.

Unique hemoglobin A1c level distribution and its relationship with mortality in diabetic hemodialysis patients.

Diabetic hemodialysis patients with hemoglobin A1c (HbA1c) levels below 6.5% and over 8.0% face a higher mortality risk. To determine the optimal glycemic control in Japanese patients, we examined the association between HbA1c and mortality in 2,300 Japanese diabetic patients on maintenance hemodialysis with HbA1c levels determined at enrollment in the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS) phases 2-5, using Cox regression analysis with adjustment for baseline age, sex, dialysis vintage, 12 general comorbidities, hemoglobin, albumin and creatinine levels, and insulin use; stratification by JDOPPS phase; and facility clustering taken into account. Overall, 54% of patients had HbA1c levels under 6.0, including 14% with HbA1c levels under 5.0. Insulin or oral diabetes medications were used less frequently in patients with higher HbA1c levels. The dependence of mortality on HbA1c level was U shaped. When the group with the lowest mortality (HbA1c 6.0-7.0) was used as a reference, the hazard ratios for HbA1c categories under 5.0, 5.0-6.0, 7.0 to under 8.0, and 8.0 and greater were, respectively, 1.56 (95% confidence interval, 1.05-2.33), 1.26 (0.92-1.71), 1.23 (0.79-1.89), and 2.10 (1.32-3.33) in the adjusted model. The HbA1c level was not associated with self-reported hypoglycemic episodes in JDOPPS phase 5. The HbA1c levels in diabetic hemodialysis patients differ considerably between Japan and those reported from Western countries. Thus, our findings highlight the importance of domestic guidelines for glycemic control by race and country.

A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. METHODS: In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2.5 and 15 mg at 4-week intervals for 12 weeks. A total of 155 SHPT patients with serum intact parathyroid hormone (iPTH) levels ≥300 pg/mL were assigned to receive etelcalcetide (n = 78) or placebo (n = 77). The primary endpoint was the proportion of patients with decreased serum iPTH to the target range proposed by the Japanese Society for Dialysis Therapy (60-240 pg/mL). The major secondary endpoint was the proportion of patients with ≥30% reductions in serum iPTH from baseline. RESULTS: The proportion of patients meeting the primary endpoint was significantly higher for etelcalcetide (59.0%) versus placebo (1.3%). Similarly, the proportion of patients meeting the major secondary endpoint was significantly higher for etelcalcetide (76.9%) versus placebo (5.2%). Serum albumin-corrected calcium, phosphorus and intact fibroblast growth factor-23 levels were decreased in the etelcalcetide group. Nausea, vomiting and symptomatic hypocalcaemia were mild with etelcalcetide. Serious adverse events related to etelcalcetide were not observed. CONCLUSIONS: This study demonstrated the efficacy and safety of etelcalcetide. As the only available intravenous calcium-sensing receptor agonist, etelcalcetide is likely to provide a new treatment option for SHPT in haemodialysis patients.

A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
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AIMS: To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. MATERIALS AND METHODS: In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. RESULTS: Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). CONCLUSIONS: Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
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A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy.

BACKGROUND: We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance. METHODS: We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively. RESULTS: 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline. CONCLUSIONS: We demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Revisiting Interdialytic Weight Gain and Mortality Association With Serum Albumin Interactions: The Japanese Dialysis Outcomes and Practice Pattern Study.

BACKGROUND: 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. DESIGN: The study type used was prospective cohort study. SUBJECTS: Patients who participated in the Japan Dialysis Outcomes and Practice Pattern Study (phase 1-4 [1999-2011]) and received thrice-weekly hemodialysis. METHODS: 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%, and >7%. sAlb was treated as both an effect modifier and confounder and dichotomized into ≥3.8 g/dL and <3.8 g/dL segments, according to the protein-energy wasting criteria proposed by the International Society of Renal Nutrition and Metabolism. MAIN OUTCOME MEASURE: The outcome in this study was all-cause mortality. RESULTS: A total of 8,661 patients were analyzed. Time-varying Cox regression analyses revealed that, when sAlb was ≥3.8 g/dL, an IDWG >7% was associated with greater risk of mortality (adjusted hazard ratio [AHR] 2.74; 95% confidence interval [CI], 1.49-5.05). When sAlb was <3.8 g/dL, however, IDWGs <2% (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 sAlb <3.8 g/dL, the mortality increased when IDWG was <3% and decreased when IDWG was between 4% and 6%. LIMITATION: The main limitation was possible residual confounding. CONCLUSIONS: 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.

Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST).

BACKGROUND: In Fabry disease, progressive glycolipid accumulation leads to damage in kidney and other organs. This study was designed to determine the prevalence rate of Fabry disease in Japanese dialysis patients. METHODS: All dialysis patients agreeing to Japan Fabry disease screening study (J-FAST) with informed consent were selected except for Fabry disease. The screening was performed by a method of measuring plasma and/or leukocytes lysosomal α-galactosidase A protein level and α-galactosidase A activity. If positive, genetic analysis was carried out upon patient's agreement. RESULTS: J-FAST dealt with 8547 patients (male 5408, female 3139). At the tertiary examination, 26 out of 8547 patients were found to be positive. Six out of 26 patients could not accept genetic analysis because of death. Remaining 20 patients agreed with genetic analysis; then 2 patients (male 2, female 0) had a variation of the α-Gal gene and 11 patients showed E66Q variations. Therefore, the frequency of Fabry disease in J-FAST was 0.04 % (2/5408) in males and 0 % (0/3139) in females, and then 0.02 % (2/8547) in all patients. The presumptive clinical diagnoses of end-stage kidney disease (ESKD) were 10 chronic glomerulonephritis, 7 diabetic nephropathy, 3 unknown etiology, 3 nephrosclerosis, 1 gouty nephropathy, 1 autosomal dominant polycystic kidney disease and 1 renal tuberculosis among 26 tertiary positive patients. Two male Fabry patients were initially diagnosed as nephrosclerosis and chronic glomerulonephritis. CONCLUSIONS: The prevalence rate of Fabry disease in J-FAST was 0.02 %. Moreover, Fabry disease could not be ruled out as the clinical diagnosis of ESKD.

Effects of protein leakage on online monitoring of ultraviolet absorbance in spent dialysate.

Recently, dialysis dose during hemodialysis treatment has been monitored by measuring the concentration of urea-like solutes such as uric acid in spent dialysate using near-ultraviolet (UV) light. The measured absorbance has been shown to have a good correlation with the time course of urea level even if the absorbance does not result from urea. However, the spent dialysate includes various solutes such as uric acid and albumin as well as unknown solutes that also absorb UV light. The effects of these solutes on monitored absorbance values are not clear. In this study, we evaluated the effect of protein leakage on data from the UV monitoring of spent dialysate. Albumin leakage in the earlier stage of the treatment may result in an increase in absorbance greater than the expected value. As a result, there is a possibility that the dialysis dose is overestimated. On the other hand, the quantity of albumin leakage could be estimated by a spent dialysate monitoring technique combined with a protein removal process.

Principal component analysis of molecularly based signals from infant formula contaminations using LC-MS and NMR in foodomics.

BACKGROUND: The challenge in developing analytical assessment of unexpected excess contaminations in infant formula has been the most significant project to address the widespread issue of food safety and security. Foodomics based on metabolomics techniques provides powerful tools for the detection of tampering cases with intentional contaminations. However, the safety and risk assessments of infant formula to reveal not only the targeted presence of toxic chemicals, but also molecular changes involving unexpected contaminations, have not been reported. In this study, a huge amount of raw molecularly based signals from infant formula was analysed using reversed phase and hydrophilic interaction chromatography with time-of-flight MS (LC-MS) and (1) H nuclear magnetic resonance (NMR) and then processed by a principal component analysis (PCA). RESULTS: PCA plots visualised signature trends in the complex signal-data batches from each excess contamination of detectable chemicals by LC-MS and NMR. These trends in the different batches from a portion of excess chemical contaminations such as pesticides, melamine and heavy metals and out-of-date products can be visualised from spectrally discriminated infant formula samples. CONCLUSION: PCA plots provide possible attempts to maximise the covariance between the stable lot-to-lot uniformity and excess exogenous contaminations and/or degradation to discriminate against the molecularly based signals from infant formulas. © 2015 Society of Chemical Industry.

Prescription of potentially inappropriate medications to elderly hemodialysis patients: prevalence and predictors.

BACKGROUND: In elderly hemodialysis (HD) patients, the risk of medication-related problems is particularly high. Thus, certain medications should generally not be prescribed to those patients. The Beers criteria for potentially inappropriate medications (PIMs) have been publicized. Still, with regard to elderly HD patients, the prevalence and risk factors for prescription of PIMs are unknown. METHODS: This was a cross-sectional study of data from the Japan Dialysis Outcomes and Practice Patterns Study (2002-08). Patients were included if they were 65 years old or older and were currently receiving HD treatment at a hospital or clinic. We counted the number of patients who were prescribed at least one PIM, as defined by the modified Beers criteria. We used multiple logistic regression analysis to determine which patient characteristics and facility characteristics were associated with prescription of PIMs. RESULTS: Data from 1367 elderly patients were analyzed. More than half of the patients (57%) had been prescribed a PIM. The three most frequently prescribed PIMs were H2 blockers (33%), antiplatelet agents (19%) and α-blockers (13%). PIM prescriptions were less likely at facilities that conducted multidisciplinary rounds {adjusted odds ratio (AOR): 0.67 [95% confidence interval (CI): 0.48-0.93]} and at teaching hospitals [AOR: 0.59 (95% CI, 0.39-0.90)]. PIM prescriptions are more likely if more than one physician has clearance to alter the HD regimen [AOR: 1.65 (95% CI, 1.12-2.44)]. CONCLUSIONS: PIMs were prescribed to many elderly HD patients in Japan. Nephrologists should become more aware of PIMs. Multidisciplinary rounds could benefit patients by reducing the prescription of PIMs.

Prevalence and incidence of chronic kidney disease stage G5 in Japan.

The prevalence and incidence of end-stage kidney disease (ESKD) have continued to increase worldwide. Japan was known as having the highest prevalence of ESKD in the world; however, Taiwan took this place in 2001, with the USA still in third position. However, the prevalence data from Japan and Taiwan consisted of dialysis patients only. The prevalence and incidence of Kidney Transplantation (KT) in Japan were quite low, and the number of KT patients among those with ESKD was regarded as negligibly small. However, the number of KT recipients has increased recently. Furthermore, there are no reports about nationwide surveys on the prevalence and incidence of predialysis chronic kidney failure patients in Japan. This review describes our recent study on the estimated number of chronic kidney disease (CKD) stage G5 patients and the number of ESKD patients living in Japan, obtained via the cooperation of five related medical societies. From the results, as of Dec 31, 2007, 275,242 patients had received dialysis therapy and 10,013 patients had a functional transplanted kidney, and as of Dec 31, 2008, 286,406 patients had received dialysis therapy and 11,157 patients had a functional transplanted kidney. Consequently, there were 285,255 patients with CKD who reached ESKD and were living in Japan in 2008 and 297,563 in 2009. We also estimated that there were 67,000 predialysis CKD stage G5 patients in 2009, 37,365 patients introduced to dialysis therapy, and 101 patients who received pre-emptive renal transplantation in this year. In total, there were 37,466 patients who newly required renal replacement therapy (RRT) in 2009. Not only the average ages, but also the primary renal diseases of the new ESKD patients in each RRT modality were different.

Differences in the Characteristics of Dialysis Patients in Japan Compared with Those in Other Countries.

BACKGROUND: Japanese patients undergoing dialysis have an extremely low mortality rate compared with those in the United States and Europe. As shown in the Dialysis Outcomes 38; Practice Patterns Study (DOPPS), certain features of dialysis treatment, such as single treatment time and amount of blood flow, are unique to Japan, but factors contributing to the low mortality risk are unclear. Although DOPPS is a multi-country prospective cohort study, the study results may not entirely reflect the real trend in Japan because the number of Japanese institutions participating in the study is small. SUMMARY: In this article, we review the data reported for Japan and other countries and reveal country-specific differences, particularly in patient age distribution and duration of dialysis. KEY MESSAGES: The mean age of prevalent dialysis patients is rising every year in Japan, and the proportion of patients undergoing dialysis for long periods of time is also increasing. In addition, the proportion of dialysis patients with diabetes, one of the primary diseases, has increased to a level similar to that observed in Western countries. However, no significant decline in the crude death rate among prevalent dialysis patients has been observed in Japan, presumably because of technological advances in dialysis treatment, but further studies are needed to elucidate the contributing factors.

Performance evaluation of developed polysulfone membrane hemodiafilters, ABH-F and ABH-P, in post- and pre-dilution hemodiafiltration.

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 ß2-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 ß2-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.

A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis.

BACKGROUND: JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. METHODS: In this Phase 3, multicenter, randomized, open-label, parallel-group study, we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis. A total of 230 patients with a serum phosphate ≥1.97 and <3.23 mmol/L were randomized to JTT-751 (dose adjusted between 1.5 and 6.0 g/day) or sevelamer hydrochloride (dose adjusted between 3.0 and 9.0 g/day) for 12 weeks. The primary outcome was change in serum phosphate from baseline to end of treatment. Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone (PTH). The changes in ferritin, transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes. RESULTS: Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group, establishing non-inferiority of JTT-751 compared with sevelamer (least squares mean, -0.03 mmol/L; 95% confidence interval, -0.13 to 0.07 mmol/L). Corrected serum calcium increased and PTH decreased from baseline within both groups; changes between groups were similar. Gastrointestinal disorders were the most common adverse events in both groups; the incidence of diarrhea was higher in the JTT-751 group, while constipation occurred frequently in the sevelamer group. Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation. CONCLUSIONS: Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia. Differential adverse effects were observed; biochemical markers of iron status increased in patients treated with JTT-751. TRIAL REGISTRATION NUMBER: CTI-111433 (The Japan Pharmaceutical Information Center at: http//www.clinicaltrials.jp). Date of registration: 7 March 2011.