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Abstract Background In chronic kidney disease (CKD), the durability of patient adherence to fluid and dietary restrictions may depend on the degree to which they have hope that they will enjoy life. Previous cross-sectional studies have shown that higher hope was associated with lower distress from fluid and dietary restrictions and better adherence in the short term. In this study, we aimed to examine the long-term relationship of hope with distress from fluid and dietary restrictions. Methods This prospective observational cohort study included 444 patients with CKD undergoing dialysis in one of five Japanese nephrology centers. Hope as a predictor was measured using an 18-item health-related hope scale. Outcomes were two-item measures of distress from fluid and dietary intake restrictions using the Japanese version of the Kidney Disease Quality of Life Short Form, Version 1.3 (higher scores indicate lower levels of distress). Multivariate linear mixed models were used to estimate the association of baseline health-related hope with distress from fluid and dietary restrictions at baseline and follow-up. Results The mean age of the participants was 67 years, and 31.1% of them were females. In total, 124, 98, and 222 had non-dialysis CKD, peritoneal dialysis, and hemodialysis, respectively. Higher levels of baseline health-related hope were associated with lower levels of distress from fluid restriction after one year (per 10-point increase, 2.6 points (95% confidence interval, 1.0 to 4.1)); whereas the baseline score was not associated with the distress from fluid restriction at 2 years. Similarly, higher levels of baseline health-related hope were associated with lower levels of distress from dietary restriction after one year (per 10-point increase, 2.0 points (95% confidence interval, 0.3 to 3.6)); whereas the baseline score was not associated with the distress from dietary restriction at 2 years. Conclusions Health-related hope, regardless of depression, can potentially mitigate long-term distress from fluid and dietary restrictions in patients with a wide range of CKD severities. Trial registration UMIN000054710.

Abstract Development of the renal medulla continues after birth to form mature renal papilla and obtain urine-concentrating ability. Here, we found that a small GTPase, Rac1, plays a critical role in the postnatal development of renal papilla. Mice with distal tubule-specific deletion of Rac1 reached adulthood but showed polydipsia and polyuria with an impaired ability to concentrate urine. The elongation of renal papilla that occurs in the first weeks after birth was impaired in the Rac1-deficient infants, resulting in shortening and damage of the renal papilla. Moreover, the osmoprotective signaling mediated by nuclear factor of activated T cells 5, which is a key molecule of osmotic response to osmotic stress in renal medulla, was significantly impaired in the kidneys of the Rac1-deficient infants. These results demonstrate that Rac1 plays an important role in the development of renal papilla in the postnatal period, and suggested a potential link between Rac1 and osmotic response.

To clarify the mechanical properties of new high heat-resistant materials, the Selective Laser Thermoregulation (SLT) method, a method of accelerated heating tests using a high-power laser, is being developed. The SLT method uses a galvano scanner to scan the surface of the area to be heated with a fiber laser, aiming to heat the sample while dynamically compensating the temperature distribution. However, the SLT method has a problem: the sample's temperature distribution fluctuates spatially and temporally due to the movement of the irradiation point of the laser, which heats the target to a high temperature. In this study, a 400 W fiber laser was scanned back and forth over the sample at scan speeds of 5, 10, and 15 m/s, respectively, and the sample temperature distribution was measured using a high-speed radiation thermometer at 1000 fps. The temperature distribution of the sample was measured using a high-speed radiation thermometer at 1000 fps. The amount of temperature increase at the laser spot was evaluated by curve fitting. The temperature increases at the laser spot decreased to 95.0, 85.1, and 75.7 K when the scan speeds were increased to 5, 10, and 15 m/s, respectively. For all scan speeds, the temperature increase at the laser spot was smaller at locations where the sample temperature was higher. The local temperature increase at the laser spot was successfully suppressed to about 4.5% of the maximum temperature of the entire sample without the laser spot. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules (PTs) purified from patients with diabetic nephropathy and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, whereas genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, whereas methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport. NEW & NOTEWORTHY: Cell type-specific DNA methylation patterns in the human kidney are not known. We examined DNA methylation in proximal tubules of patients with diabetic nephropathy and revealed that oxidative stress, cytoskeleton, and metabolism genes were aberrantly methylated. The results indicate that aberrant DNA methylation in proximal tubules underlies kidney dysfunction in diabetic nephropathy. Aberrant methylation could be a target for reversing memory of poor glycemic control. [ABSTRACT FROM AUTHOR]

This study investigates the effectiveness of a globally popular method of self-learning at the right level in improving learning outcomes—the cognitive and noncognitive abilities of disadvantaged students—in a developing country, Bangladesh. Using a randomized controlled trial design, we find substantial improvements in cognitive abilities measured by math test scores and in catch-up effects in terms of noncognitive abilities or personality traits measured through a self-esteem scale. Moreover, our study is, to our knowledge, the first to use alternative cognitive ability measures, that is, time reduction as well as time-adjusted test score, which are critical dimensions of cognitive development. Subsequently, we investigate the long-term effects using students' math results in the national-level exam. We find a reasonable longer-term effect on cognitive abilities 20 months after the intervention for younger students. Our estimates indicate that the program's benefits exceed its costs. [ABSTRACT FROM AUTHOR]

Abstract Background In chronic kidney disease (CKD), patients’ adherence to prescriptions for diet and for medications might depend on the degree to which they have hope that they will enjoy life, and that hope could vary with the stage of CKD. The aims of this study were to quantify both the association of CKD stage with health-related hope (HR-Hope), and the association of that hope with psychological and physiological manifestations of adherence. Methods This was a cross-sectional study involving 461 adult CKD patients, some of whom were receiving dialysis. The main exposure was HR-Hope, measured using a recently-developed 18-item scale. The outcomes were perceived burden of fluid restriction and of diet restriction, measured using the KDQOL, and physiological manifestations of adherence (systolic and diastolic blood pressure [BP], and serum phosphorus and potassium levels). General linear models and generalized ordered logit models were fit. Results Participants at non-dialysis stage 4 and those at stage 5 had lower HR-Hope scores than did those at stage 2 or 3 (combined). Those at non-dialysis stage 5 had the lowest scores. HR-Hope scores of participants at stage 5D were similar to those of participants at stage 4, but they were lower than the scores of participants at stage 2 or 3 (combined). Higher HR-Hope scores were associated with lower perceived burdens of fluid restriction and of diet restriction (adjusted ORs per ten-point difference were 0.82 and 0.84, respectively). Higher HR-Hope scores were associated with lower systolic BP (adjusted mean difference in systolic BP per ten-point difference in HR-Hope scores was − 1.87 mmHg). In contrast, HR-Hope scores were not associated with diastolic BP, serum phosphorus levels, or serum potassium levels. Conclusions Among CKD patients, HR-Hope is associated with disease stage, with psychological burden, and with some physiological manifestations of adherence.

Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II-induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II-induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II-induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A2 analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation., Introduction Aging is a progressive accumulation of changes in the body that increases susceptibility to disorders such as Alzheimer's disease, cerebrovascular disease, diabetes, and cardiovascular disease, including hypertension. Hypertension is [...]

Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP

Abstract In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Rationale & Objective: Depression is prevalent and highly associated with mortality among patients with chronic kidney disease (CKD). Psychological flexibility can be captured as acceptance in psychology, and its improvement by behavioral therapy is associated with reduced depression in some clinical settings. However, no study has been reported on patients with CKD. This study aimed to examine the association between psychological flexibility and depression in patients with CKD. Study Design: Cohort study. Setting & Participants: This multicenter study of 5 hospitals in Japan included patients with nondialysis stage 3-5 CKD or stage 5D CKD receiving hemodialysis or peritoneal dialysis. Predictor: Psychological flexibility measured using the 7-item Acceptance and Action Questionnaire (AAQ-II). Outcomes: The prevalence and incidence of depression after 1 year, which was defined by a score ≥ 16 points on the Center for Epidemiologic Studies Depression (CES-D) questionnaire. Analytical Approach: Gamma regression was used in the examination of correlates of the psychological flexibility value. Modified Poisson regression models were fit for the prevalence and incidence of depression. Results: The cross-sectional and longitudinal analyses included 433 and 191 patients, respectively. Lower (ie, worse) psychological flexibility levels were associated with hemodialysis and peritoneal dialysis. Higher (ie, better) psychological flexibility levels were associated with lower prevalence of depression (per 5-point increase; adjusted prevalence ratio, 0.75; 95% CI, 0.70-0.80) and lower incidence of depression (per 5-point increase; adjusted risk ratio, 0.72; 95% CI, 0.61-0.85). Limitations: Depression was assessed using the CES-D questionnaire. Cultural differences may exist in the interpretation of AAQ-II scores. Conclusions: Better psychological flexibility was associated with lower prevalence and incidence of depression in patients with CKD. Further studies are warranted to determine the possible prevention and treatment of depression by the development of behavioral interventions to improve psychological flexibility.

Introduction Renal tubular injury contributes to the decline in kidney function in patients with diabetes. Cell type-specific DNA methylation patterns have been used to calculate proportions of particular cell types. In this study, we developed a method to detect renal tubular injury in patients with diabetes by detecting exfoliated tubular cells shed into the urine based on tubular cell-specific DNA methylation patterns.Research design and methods We identified DNA methylation patterns specific for human renal proximal tubular cells through compartment-specific methylome analysis. We next determined the methylation levels of proximal tubule-specific loci in urine sediment of patients with diabetes and analyzed correlation with clinical variables.Results We identified genomic loci in SMTNL2 and G6PC to be selectively unmethylated in human proximal tubular cells. The methylation levels of SMTNL2 and G6PC in urine sediment, deemed to reflect the proportion of exfoliated proximal tubular cells due to injury, correlated well with each other. Methylation levels of SMTNL2 in urine sediment significantly correlated with the annual decline in estimated glomerular filtration rate. Moreover, addition of urinary SMTNL2 methylation to a model containing known risk factors significantly improved discrimination of patients with diabetes with faster estimated glomerular filtration rate decline.Conclusions This study demonstrates that patients with diabetes with continual loss in kidney function may be stratified by a specific DNA methylation signature through epigenetic urinalysis and provides further evidence at the level of exfoliated cells in the urine that injury of proximal tubular cells may contribute to pathogenesis of diabetic kidney disease.

Abstract Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db compared with control. Given downregulation of Tgfb1 expression by folic acid, antioxidant Tempol reversed DNA demethylation, with increased and decreased recruitment of DNMT1 and USF1 to the promoter, resulting in decreased Tgfb1 expression in db/db mice. Addition of H2O2 to mesangial cells induced DNA demethylation and upregulated Tgfb1 expression. Finally, Tempol attenuated mesangial fibrosis in db/db mice. We conclude that aberrant DNA methylation of Tgfb1 due to ROS overproduction play a key to mesangial fibrosis during DN progression.

Abstract Background Serum albumin is a marker of nourishment and inflammation. Although hypoalbuminemia in hemodialysis patients is reported as a risk factor for poor prognosis, few studies describe its effects on infectious diseases specifically. This study aimed to examine the relationship between the serum albumin level on admission and infection-related in-hospital death among hemodialysis patients. Methods This was a multicenter retrospective observational study that was undertaken in Japan. We reviewed the medical records of 507 hemodialysis patients aged > 18 years, whose blood cultures were obtained based on suspicion of infectious disease, and who were managed at seven Japanese tertiary dialysis units from August 2011 to July 2013. The outcome measure was infection-related in-hospital death. Multivariate logistic regression models adjusted for age, sex, the dialysis vintage, diabetes mellitus, bacteremia, and log C-reactive protein levels were used for the statistical analysis. Results Four hundred patients were analyzed and allocated to three groups based on their serum albumin levels: marked hypoalbuminemia (

Background: Large-scale clinical trials have analyzed risk factors for any ischemic stroke in patients with atrial fibrillation (AF). However, the risk factors for cardioembolic stroke (CES), specifically, have not been reported. To clarify the risk factors for CES and clinically significant cardioembolic infarction, we examined the incidence of CES and larger infarct volume (IV) (> 30 mL) CES, employing the Fushimi AF Registry, a community-based prospective cohort of AF patients in the Fushimi ward, Kyoto, Japan. Methods: A total of 4,182 Fushimi AF patients were enrolled from March 2011 to December 2014. The risk factors for CES were evaluated using multivariate analysis. Results: Of 4,182 patients enrolled, 3,749 patients were observed for ≥1 year. During the follow-up period (mean duration, 979 ± 7.7 days), 91/3,749 patients experienced a CES (2.43%). Significant risk factors associated with CES were older age (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01–1.72; p = 0.046), low body weight (OR, 1.30; 95% CI, 1.03–1.65; p = 0.033), sustained AF (OR, 1.67; 95% CI, 1.05–2.71; p = 0.034), and previous stroke or transient ischemic attack (TIA) (OR, 1.94; 95% CI, 1.22–3.06; p = 0.004). Predictors of a large IV were chronic kidney disease (CKD) (OR, 2.08; 95% CI, 1.09–4.05; p = 0.027) and previous stroke/TIA (OR, 2.27; 95% CI, 1.19–4.24; p = 0.011). Conclusions: In this population-based cohort of Japanese patients with AF, in addition to previous stroke/TIA and older age, sustained AF and low body weight emerged as risk factors for CES, as opposed to any stroke, which may have a different risk profile. Patients with CKD or previous stroke/TIA who developed cardioembolic infarction exhibited more advanced severity. There is a need for direct oral anticoagulants that can be used safely in patients with comorbid AF and CKD.