Japan's cancer survivorship guidelines for exercise and physical activity.

OBJECTIVE: This research aimed to establish the inaugural evidence-based cancer survivorship guidelines for Japan, with a particular focus on exercise and physical activity, in order to enhance health outcomes for cancer survivors. METHODS: A panel of experts, including oncologists, physicians, exercise scientists, epidemiologists and patient advocates, utilized a modified Delphi process and systematic reviews to establish consensus on exercise recommendations for cancer survivors. The panel focused on setting the objectives of the Clinical Practice Guidelines and addressing crucial clinical issues in Japan. Recommendations were formulated based on the strength and certainty of evidence, the benefit-harm balance and patient values and preferences. RESULTS: The panel formulated exercise recommendations for cancer survivors of two age groups: 18-64 years and ≥65 years. The recommendations for both age groups are consistent, emphasizing the importance of regular exercise and physical activity tailored to individual capabilities and health conditions. The guidelines underline the benefits of exercise in improving the overall health and quality of life of cancer survivors. This consensus on exercise recommendations marks a significant step in the development of comprehensive cancer survivorship guidelines in Japan, with potential implications for improving clinical outcomes and advancing research in cancer survivorship. CONCLUSIONS: These guidelines will serve as a critical resource for cancer survivors, highlighting exercise as a key component of survivorship care, and for clinicians, in recommending appropriate physical activities to improve survivor health and well-being.

Erythropoiesis-stimulating agents for preventing acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is characterised by a rapid decline in kidney function and is caused by a variety of clinical conditions. The incidence of AKI in hospitalised adults is high. In animal studies, erythropoiesis-stimulating agents (ESA) have been shown to act as a novel nephroprotective agent against ischaemic, toxic, and septic AKI by inhibiting apoptosis, promoting cell proliferation, and inducing antioxidant and anti-inflammatory responses. As a result, ESAs may reduce the incidence of AKI in humans. Randomised controlled trials (RCTs) have been conducted on the efficacy and safety of ESAs, but no prior systematic reviews exist that comprehensively examine ESAs with respect to AKI prevention, although the effectiveness of these agents has been examined for a range of other diseases and clinical situations. OBJECTIVES: This review aimed to look at the benefits and harms of ESAs for preventing AKI in the context of any health condition. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 30 August 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included RCTs and quasi-RCTs (in which allocation to treatment was based on alternate assignment or order of medical records, admission dates, date of birth or other non-random methods) that compared ESAs with placebo or standard care in people at risk of AKI. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias for included studies. We used random-effects model meta-analyses to perform quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each main outcome using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: A total of 20 studies (36 records, 5348 participants) were included. The number of participants ranged from 10 to 1302, and most studies were carried out in single centres (13/20). All the included studies compared ESAs to placebo or usual care. Many of the studies were judged to have unclear or high risk of reporting bias, but were at low risk for other types of bias. ESAs, when compared to control interventions, probably makes little or no difference to the risk of AKI (18 studies, 5314 participants: RR 0.97, 95% CI 0.85 to 1.10; I² = 19%; moderate-certainty evidence), or death (18 studies, 5263 participants: RR 0.92, 95% CI 0.80 to 1.06; I² = 0%; moderate-certainty evidence), and may make little or no difference to the initiation of dialysis (14 studies, 2059 participants: RR 1.16, 95% CI 0.90 to 1.51; I² = 0%; low-certainty evidence). Even with standardised measurement of AKI, the studies showed no difference in results between different routes of administration (subcutaneous or intravenous), background diseases (cardiac surgeries, children or neonates, other adults at risk of AKI), or duration or dose of ESA. ESAs may make little or no difference to the risk of thrombosis when compared to control interventions (8 studies, 3484 participants: RR 0.92, 95% CI 0.68 to 1.24; I² = 0%). Similarly, ESAs may have little or no effect on kidney function measures and adverse events such as myocardial infarction, stroke or hypertension. However, this may be due to the low incidence of these adverse events. AUTHORS' CONCLUSIONS: In patients at risk of AKI, ESAs probably do not reduce the risk of AKI or death and may not reduce the need for starting dialysis. Similarly, there may be no differences in kidney function measures and adverse events such as thrombosis, myocardial infarction, stroke or hypertension. There are currently two ongoing studies that have either not been completed or published, and it is unclear whether they will change the results. Caution should be exercised when using ESAs to prevent AKI.

Recipients of public assistance with advanced chronic kidney disease: insights into receiving a presentation of kidney replacement therapy options and polypharmacy from Japanese investigators with innovative network about kidney disease study.

BACKGROUND: The characteristics of patients with advanced chronic kidney disease (CKD) who are recipients of public assistance in Japan, and the adequacy of their medical care have not been reported previously. METHODS: The records of patients with CKD stage G5 who visited nine facilities in Japan from April to June 2013 were retrospectively reviewed to compare the characteristics and care of recipients of public assistance with those of non-recipients. Receiving a presentation of kidney replacement therapy (KRT) options and polypharmacy were used as indicators of suboptimal medical care. RESULTS: Of the 592 patients included in this analysis (mean age, 69.6 years; male, 59.3%), 56 (9.5%) were recipients of public assistance and 536 (90.5%) were non-recipients of public assistance. The prevalence of diabetes mellitus, unmarried status, and living alone were higher in recipients of public assistance. In multivariable logistic regression analysis, compared with non-recipients of public assistance, recipients of public assistance were less likely to receive a presentation of KRT options (adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.17-0.56), and were more likely to receive ≥ 10 (aOR, 1.92; 95% CI, 1.05-3.51), and ≥ 15 (aOR, 2.78; 95% CI, 1.23-6.26) types of medication. CONCLUSIONS: Patients with advanced CKD receiving public assistance were less likely to receive a presentation of KRT options and more likely to receive ≥ 10 and ≥ 15 types of medication, suggesting that recipients of public assistance are more likely to receive suboptimal medical care.

Management of anaemia and prognosis of patients undergoing maintenance peritoneal dialysis: A nationwide cohort study.

BACKGROUND: Clinical data supporting the target haemoglobin range in patients undergoing peritoneal dialysis (PD) are scarce. This study investigated the association between haemoglobin levels and all-cause mortality in Japanese patients undergoing PD using data from a nationwide dialysis registry. METHODS: A total of 4875 patients aged ≥18 years who were undergoing PD at the end of 2012 were analysed. Patients receiving combination therapy with haemodialysis or missing haemoglobin data were excluded. Haemoglobin values were categorised into six groups (<9.0, 9.0-9.9, 10.0-10.9, 11.0-11.9, 12.0-12.9 and ≥13.0 g/dL) and their association with mortality evaluated. RESULTS: Patients' mean age was 63 years, and 62% were men. The mean haemoglobin level was 10.7 g/dL, and 14% were anuric. Erythropoiesis-stimulating agents were used in 89%. During a median follow-up of 3.5 years, 1586 patients died. Haemoglobin levels <9.0 and ≥13.0 g/dL were significantly associated with mortality, as compared with levels of 10.0-10.9 g/dL (adjusted hazard ratios [95% confidence intervals]: 1.25 [1.06-1.48] and 1.45 [1.13-1.88], respectively). Restricted cubic spline analysis revealed a U-shaped association between haemoglobin levels and mortality. A haemoglobin level ≥12 g/dL was associated with mortality in patients with a history of cardiovascular disease (p interaction = 0.023). CONCLUSION: We provide important insights into the target haemoglobin in patients undergoing PD. Our findings suggest that setting a lower upper limit for haemoglobin levels may be beneficial for patients with a history of cardiovascular disease.

Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.

A case of spontaneous coronary artery dissection that later turned out to be Takayasu arteritis.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), which typically occurs in women at low risk of atherosclerosis. We herein report a case of SCAD in a 57-year-old man who later developed Takayasu arteritis. The patient presented to our hospital complaining of chest pain and was diagnosed with unstable angina. Emergent coronary angiography was performed, and optical coherence tomography revealed that ACS was caused by SCAD. The patient was treated medically without further ballooning or stenting. Because there was a bilateral difference in blood pressure, the systemic artery was screened by contrast-enhanced computed tomography, which showed left subclavian artery occlusion, proximal stenosis of the superior mesenteric artery, right common iliac artery dissection, and left external iliac artery dissection. Based on these results and 18F-fluorodeoxyglucose positron emission tomography findings, we diagnosed Takayasu arteritis. Prednisolone and tocilizumab were selected for medical treatment, and the patient was in a good condition at one year after the diagnosis. Takayasu arteritis can cause dissection of various arteries and should be suspected when atypical SCAD or multiple dissections are present. Early initiation of immunosuppressive therapy can control disease activity. Learning objective: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome. In this case, we experienced a case of SCAD which turned out to be the first symptom of Takayasu arteritis. Immunosuppressive therapy was effective for both coronary lesion and systemic vasculitis. Not only fibromuscular dysplasia, but also various types of vasculitis should therefore be considered in the differential diagnosis when encountering atypical SCAD cases.

Exercise instruction during haemodialysis treatment after changes to the insurance regime: a nationwide questionnaire survey in Japan.

In April 2022, an additional medical fee for exercise instruction during haemodialysis treatment was approved for insurance claims in Japan. We conducted a questionnaire survey to investigate the current situation regarding exercise therapy during haemodialysis treatment after this change. Questionnaires were mailed to 4257 haemodialysis facilities, almost all the haemodialysis facilities in Japan, on January 31, 2023. In total, 1657 facilities responded, of which 550 (33%) provided exercise instruction during haemodialysis treatment, and 65% of these claimed the new fee. Of the 550 facilities that had claimed the fee at the time of survey, 245 (55%) started exercise instruction in April 2022 or later. Exercise instruction focused on resistance training (81%) and aerobic exercise (62%) for 20-30 min (66%) three times a week (80%). The instructors included physicians in 45% of facilities, nurses in 74%, and physical therapists in 36%. Efficacy was evaluated in 76% of the facilities providing instruction, mainly by assessing change in muscle strength (49%). Overall, 39% of facilities had experienced some adverse events, but none were life-threatening. In conclusion, after the change in the insurance regime, exercise instruction during haemodialysis treatment has become more popular, and more patients on haemodialysis are undergoing exercise therapy.

The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study.

INTRODUCTION: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. METHODS: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. RESULTS: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57). CONCLUSIONS: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.

Preference for anti-phospholipase A2 receptor antibody assay in patients with suspected membranous nephropathy: a survey study on medical practice after publication of Japanese Guidelines for Nephrotic Syndrome 2020.

BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test. METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation. RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation. CONCLUSION: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists.

BACKGROUND: Although rituximab (RTX) is recommended by kidney disease improving global outcomes as one of the standard therapies for primary membranous nephropathy (pMN), given the constraint of insurance coverage, it is not clear how the drug is used in Japan. METHODS: This cross-sectional study was conducted via a web-based survey between November and December 2021. The participants were certified nephrologists and recruited through convenience sampling. Experience with RTX for pMN was compared to experience with RTX for minimal change nephrotic syndrome (MCNS). Reasons for withholding RTX for pMN, even when it is indicated, were also investigated. Furthermore, the proportion difference in RTX experience was analyzed. RESULTS: Responses from 380 nephrologists across 278 facilities were analyzed. RTX was used for pMN by 83 (21.8%), which was less than the 181 (47.6%) who had used RTX for MCNS (ratio of proportions: 0.46). RTX use for pMN was more frequent in facilities performing 41-80 and 81 or more kidney biopsies annually (vs. none) and by physicians with experience in anti-PLA2R antibody measurement. RTX administration for pMN was covered by insurance for 56 (67.5%), was facility-paid for 10 (12.0%), and was copaid by patients for 6 (7.2%). The most common reason for withholding RTX for pMN was difficulty in ensuring financing (146, 79.3%). CONCLUSIONS: RTX use for pMN is less common than for MCNS but not infrequent. Treatment with RTX was more frequent in biopsy-intensive facilities, and it was fully paid by the facility or patient in one-fifth of cases.

Association between urinary C-megalin levels and progressive kidney dysfunction: a cohort study based on the diabetes distress and care registry at Tenri (DDCRT 24).

AIMS: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. METHODS: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. RESULTS: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. CONCLUSIONS: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs.

Clinical utility of diaphragmatic ultrasonography for mechanical ventilator weaning in adults: A study protocol for systematic review and meta-analysis.

Background and Aims: Mechanical ventilation is associated with several risks, including barotrauma, ventilator-associated pneumonia, and ventilator-induced diaphragmatic dysfunction. A delay in weaning from mechanical ventilation increases these risks, and prolonged weaning has been shown to increase hospital mortality. Various tools have been used in clinical practice to predict successful weaning from mechanical ventilation; however, they have a low prognostic accuracy. The use of ultrasonography in intensive care units is an area of growing interest since it is a noninvasive, convenient, and safe modality. Since ultrasonography can provide real-time assessment of diaphragmatic morphology and function, it may have clinical utility in predicting successful mechanical ventilator weaning. This study aimed to describe a protocol to assess the effectiveness of diaphragmatic ultrasonography in the decision-making process for ventilator weaning in terms of its impact on clinical outcomes. Methods: This systematic review of published analytical research will use an aggregative thematic approach according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will perform a comprehensive search for studies on the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Two authors will independently perform abstract and full-text screening and data extraction. Additionally, a meta-analysis and the risk of bias evaluation will be conducted, as appropriate. Conclusion: Systematic reviews on the effectiveness of diaphragmatic ultrasonography in the decision-making process for ventilator weaning in terms of its impact on clinical outcomes are lacking. The results of this systematic review may serve as a basis for future clinical trials. Systematic review registration: This protocol was registered with the Open Science Framework: https://osf.io/cn8xf.

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

Outcomes of discontinuing renin-angiotensin system inhibitors: a study protocol for conducting systematic review and meta-analysis.

INTRODUCTION: Renin-angiotensin system (RAS) plays a key role in various types of cardiovascular disease and many kinds of RAS inhibitors have been developed. The effect of discontinuation of RAS inhibitors on clinical outcomes is still controversial. This study aims to evaluate the effects of discontinuing RAS inhibitor medication on the clinical outcomes of patients continuously taking these agents. METHODS AND ANALYSIS: This article presents a systematic review protocol described in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include randomised controlled trials in which the effects of RAS inhibitor withdrawal were evaluated. Initially, four authors will search for eligible studies in MEDLINE, EMBASE, the Cochrane Database Trial Register, European trial registry and ClinicalTrials.gov. Abstracts and full-text screenings will be performed by the four authors with data extraction performed by each author independently. We will include patients taking RAS inhibitors-including ACE inhibitor, angiotensin receptor blocker and angiotensin receptor neprilysin inhibitor and exclude the patients undergoing renal replacement therapy (RRT), adolescents (under 18 years of age) and patients with acute infectious diseases. Our search will be performed on 1 May 2023. Studies in which the patients discontinued RAS inhibitors due to any reason will be included. Patients who continuously took RAS inhibitors under conditions in which the intervention group discontinued these agents will be considered eligible as the comparison group. Death (any cause), Death (cardiovascular disease (CVD)) and CVD events will be set as primary outcomes. Secondary outcomes will be set as RRT, acute kidney injury, renal function (analysis of the change in estimated glomerular filtration rate), hyperkalaemia, proteinuria and blood pressure. ETHICS AND DISSEMINATION: Research ethics approval was not required in this study due to it being a systematic review, and any data belonging to individuals cannot be identified. The results of this study will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: PROSPERO CRD42022300777.

Hyponatremia and mortality in patients undergoing maintenance hemodialysis: Systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis examined the relationship between hyponatremia and worse outcomes in patients undergoing maintenance hemodialysis. METHODS: The MEDLINE, EMBASE, CENTRAL, and Web of Science databases were used to search for relevant articles. The target population was patients on maintenance hemodialysis (those undergoing hemodialysis for ≥60 days). The defined outcomes were death, cardiovascular disease, cognitive decline, and falls. Meta-analysis was performed with a random-effects model of pairwise comparisons of normonatremia and hyponatremia defined for each study, 1-mmol/L increment of sodium analysis, and dose-response analysis using the sodium concentration defined for each study. This study was registered with PROSPERO (registration number CRD42018087667). RESULTS: Thirteen articles were included. The pairwise analysis revealed that the hazard ratio for all-cause mortality was 1.45 (95% confidence interval, 1.31-1.61). The analysis of 1-mmol/L increment of sodium included six studies with a hazard ratio for all-cause mortality of 0.94 (95% confidence interval, 0.91-0.97) for each 1-mmol/L increase in the serum sodium concentration. In the dose-response analysis, assuming a linear relationship, a sodium increment of 1 mmol/L revealed a hazard ratio for all-cause mortality of 0.97 (95% confidence interval, 0.96-0.98). Other outcomes could not be integrated. CONCLUSIONS: Hyponatremia is associated with all-cause mortality in patients undergoing maintenance hemodialysis. Healthcare providers should pay special attention to even the slightest indication of hyponatremia.

Initiation of renin-angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study.

BACKGROUND: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. METHODS: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR. RESULTS: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively. CONCLUSION: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy.

Adherence to methotrexate and associated factors considering social desirability in patients with rheumatoid arthritis: a multicenter cross-sectional study.

BACKGROUND: Assessing medication adherence in rheumatoid arthritis (RA) is clinically significant as low adherence is associated with high disease activity. Self-reported medication adherence surveys have been shown to have problems with overestimation of adherence due to social desirability bias. However, no MTX adherence studies adjusted for social desirability have been conducted to date. This study aimed to evaluate adherence to MTX and perform an investigatory search for factors associated with MTX adherence including social desirability. METHODS: This cross-sectional multicenter study was conducted among adult RA patients consuming oral MTX for ≥ 3 months. We examined the distribution of MTX adherence, according to the eight-item Morisky Medication Adherence Scale (MMAS-8). Social desirability was using the Social Desirability Scale (SDS). Furthermore, an exploratory factor analysis involving social desirability was examined to identify factors associated with MTX adherence using linear regression analysis. To deal with missing values, we used multiple imputations with chained equations methods. RESULTS: A total of 165 RA patients were enrolled. The median age was 64 years, and 86.1% were women. Based on the MMAS-8, low, medium, and high adherences were noted in 12.1%, 60.0%, and 27.9% of participants, respectively. High social desirability (coefficient, 0.14; 95% confidence interval [CI], 0.05-0.23; p < 0.05) and high age (coefficient per 10 years, 0.16; 95% CI, 0.01-0.03; p < 0.05) were associated with high MTX adherence, whereas full-time work was negatively associated with high MTX adherence (coefficient, -0.50; 95% CI, -0.95--0.05; p < 0.05). CONCLUSIONS: A large proportion of patients with RA do not take MTX as prescribed. High social desirability, high educational level, and non-full-time work may be associated with high MTX adherence. Physicians should confirm MTX adherence before switching or adding disease-modifying anti-rheumatic drugs in cases of uncontrolled disease activity.

Urinary C-megalin as a novel biomarker of progression to microalbuminuria: A cohort study based on the diabetes Distress and Care Registry at Tenri (DDCRT 22).

AIMS: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus. METHODS: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model. RESULTS: During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07-1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10-<30 mg/gCr) UACR. CONCLUSIONS: Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation.

Biopsy-proven Streptococcus suis-associated Infectious Glomerulonephritis.

A 64-year-old Japanese man who worked at a butcher shop was hospitalized for a fever, headache, and deafness. We diagnosed him with sepsis and meningitis caused by Streptococcus suis infection. The patient's renal function declined rapidly, and hemodialysis was performed temporarily. A renal biopsy was performed, and the renal function tended to improve with antimicrobial therapy. This case seemed rather similar to one of staphylococcal-associated nephritis in that it showed mesangial proliferative nephritis with immunoglobulin A deposition, even though the nephritis was caused by streptococci. Similarly, intramembranous electron-dense deposits were characteristic findings. We present new findings of an in vivo renal biopsy in a case of S. suis-associated glomerulonephritis.