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.

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.

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.

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.

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.

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.

Aldosterone antagonists for people with chronic kidney disease requiring dialysis.

BACKGROUND: People with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular death and morbidity. Several clinical studies suggested that aldosterone antagonists would be a promising treatment option for people undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for people with CKD on dialysis has yet to be determined. OBJECTIVES: This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in people with CKD requiring haemodialysis (HD) or peritoneal dialysis (PD). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 5 August 2020 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 Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), cross-over RCTs, and quasi-RCTs (where group allocation is by a method that is not truly random, such as alternation, assignment based on alternate medical records, date of birth, case record number, or other predictable methods) that compared aldosterone antagonists with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I² statistic to measure heterogeneity among the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 16 studies (14 parallel RCTs and two cross-over RCTs) involving a total of 1446 participants. Thirteen studies compared spironolactone to placebo or standard care and one study compared eplerenone to a placebo. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists probably reduced the risk of death (any cause) for people with CKD requiring dialysis (9 studies, 1119 participants: RR 0.45, 95% CI 0.30 to 0.67; I² = 0%; moderate certainty of evidence). Aldosterone antagonist probably decreased the risk of death due to cardiovascular disease (6 studies, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I² = 0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 studies, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I² = 0%; moderate certainty of evidence). While aldosterone antagonists probably increased risk of gynaecomastia compared with control (4 studies, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I² = 0%; moderate certainty of evidence), aldosterone antagonists may make little or no difference to the risk of hyperkalaemia (9 studies, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I² = 47%; low certainty of evidence). Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (8 studies, 633 participants: SMD -0.42, 95% CI -0.78 to 0.05; I² = 77%). In people with CKD requiring dialysis received aldosterone antagonists compared to control, there were 72 fewer deaths from all causes per 1000 participants (95% CI 47 to 98) with a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 10 to 21) and for gynaecomastia were 26 events per 1000 participants (95% CI 15 to 39) with a number need to treat for an additional harmful outcome (NNTH) of 38 (95% CI 26 to 68). AUTHORS' CONCLUSIONS: Based on moderate certainty of the evidence, aldosterone antagonists probably reduces the risk of all-cause and cardiovascular death and probably reduces morbidity due to cardiovascular and cerebrovascular disease in people with CKD requiring dialysis. For the adverse effect of gynaecomastia, the risk was increased compared to control. For this outcome, the absolute risk was lower than the absolute risk of death. It is hoped the three large ongoing studies will provide better certainty of evidence.

Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study.

BACKGROUND: Metabolic acidosis, which reduces serum bicarbonate levels, contributes to the progression of chronic kidney disease (CKD). The difference between sodium and chloride (Na-Cl) may theoretically predict serum bicarbonate levels. This study aimed to evaluate serum Na-Cl level as a risk factor for renal function decline among patients who participated in the chronic kidney disease Japan cohort (CKD-JAC) study. METHODS: The association between low Na-Cl concentration (< 34 mmol/L) and composite renal function decline events (any initiation of renal replacement therapy or 50% decline in estimated glomerular filtration rate) was evaluated among 2143 patients with CKD stage G3a-4. Using Cox regression analysis, hazard ratios (HRs) were estimated after adjusting for the following covariates: age, sex, diabetes mellitus, diabetic nephropathy, cardiovascular disease, anemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, loop diuretics, cigarette smoking, body mass index, serum albumin, systolic blood pressure, urine albumin-to-creatinine ratio, and CKD stage. RESULTS: Composite renal function decline events were observed in 405 patients (18.9%) over the 4-year follow-up period. Low serum Na-Cl level (< 34 mmol/L) was independently associated with a greater risk for composite renal function decline events (HR 1.384; 95% confidence interval [CI], 1.116-1.717). Subgroup analyses identified that the association between low Na-Cl level and composite renal function decline events was stronger among patients with CKD stage G4 and those with anemia. CONCLUSIONS: Our investigation suggests that Na-Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia.

Variations in actual practice patterns and their deviations from the clinical practice guidelines for nephrotic syndrome in Japan: certified nephrologists' questionnaire survey.

BACKGROUND: Few good-quality clinical trials on adults with nephrotic syndrome exist. Thus, there are discrepancies between real-world practice and clinical practice guidelines. We conducted a questionnaire-based survey to investigate potential discrepancies and the factors associated with variations in clinical practice. METHODS: A questionnaire was administered electronically to all board-certified nephrologists in Japan. To examine clinical practice variations in relation to physician characteristics, we estimated the ratio of the mean duration of steroid therapy using a generalized linear model, and the odds ratio of higher level ordinal variables using an ordered logistic regression model. RESULTS: Responses of the 116 participants showed some variation for the majority of questions. Most participants (94.8%) indicated that screening for malignant tumors was "Conducted for almost all patients". The duration of steroid therapy was found to be longer among physicians seeing ≥ 30 patients with nephrotic syndrome per month, both for minimal-change disease (ratio of mean 1.69; 95% CI 1.07-2.66) and membranous nephropathy (ratio of mean 1.71; 95% CI 1.09-2.69). CONCLUSIONS: We identified practice patterns for nephrotic syndrome and discrepancies between clinical practice guidelines and actual practice. Defining the standard therapy for nephrotic syndrome may be necessary to generate high-quality evidence and develop clinical guidelines.

Impact of salt taste dysfunction on interdialytic weight gain for hemodialysis patients; a cross-sectional study.

BACKGROUND: Little is known about salt taste dysfunction among hemodialysis (HD) patients. This study aimed to elucidate the prevalence of salt taste dysfunction and its relationship with interdialytic weight gain (IDWG) among HD patients. METHODS: A single-center cross-sectional study involving 99 maintenance HD patients was conducted in September 2015. Salt taste threshold was measured using a salt-impregnated test strip. Salt taste dysfunction was defined as a recognition threshold of ≥0.8%. IDWG was calculated as the mean value of weight gain at the beginning of each week during a 1-month period before the taste test. We performed a multivariate analysis using the standard linear regression model to investigate the association between salt taste dysfunction and IDWG. RESULTS: Among the 99 participants, 42% had a recognition threshold of 0.6%, whereas 38% had a recognition threshold of ≥1.6%. Overall, the prevalence of salt taste dysfunction was 58%. The mean (±SD) IDWG was 4.9% (±1.7%), and there was no significant difference in IDWG between the two groups with (4.9%) and without (4.8%) salt taste dysfunction (P = 0.90). A multivariate analysis indicated that salt taste dysfunction is not significantly associated with IDWG (mean difference = 0.06; 95% confidence interval = - 0.27 to 0.40). CONCLUSIONS: The prevalence of salt taste dysfunction was very high among HD patients who had a unique distribution of salt taste recognition thresholds with two peaks. We found no significant association between salt taste dysfunction and IDWG.

Practice pattern of physician's directions of exercise restriction in patients with chronic kidney disease: results from the Chronic Kidney Disease Japan Cohort study.

BACKGROUND: The practice patterns of exercise restrictions for patients with chronic kidney disease have not been adequately evaluated yet; thus, we examined them using a cross-sectional design and explored the factors related with those restrictions. METHODS: The Chronic Kidney Disease Japan Cohort study was a multicentre cohort study of Japanese patients (age 20-75 years) living in Japan. We used the information in the questionnaire on the restriction of physical activities offered by physicians to the patients during enrolment. We initially considered and used the following data as the clinical factors that the physician used for decision making on the directions of restriction of physical activities: age, sex, cause of chronic kidney disease (CKD), comorbid diseases, body mass index (BMI), systolic blood pressure, estimated glomerular filtration rate (eGFR) and urine albumin. The logistic regression model was used to explore the factors and estimate their adjusted odds ratio with regard to physician's direction of restriction of physical activities. RESULTS: Physician's direction of exercise restrictions was implemented in 9.9% of the participants. In 17 facilities, the proportion of physician's direction of exercise restriction ranged from 2.9 to 17.8%. The logistic regression analysis showed that the proportion of the factors such as younger age, cardiovascular disease, congestive heart failure and lower eGFR was higher in patients with physician's direction of exercise restrictions. CONCLUSIONS: The findings from this study suggested the factors related with prescribing exercise restrictions. Further studies examining which patients with CKD need direction of exercise restrictions are needed.

Impact of the new risk stratification in the 2011 Japanese Society of Nephrology clinical guidelines for IgA nephropathy on incidence of early clinical remission with tonsillectomy plus steroid pulse therapy.

BACKGROUND: In 2011, the Japanese Society of Nephrology (JSN) published new clinical guidelines for IgA nephropathy (IgAN) with a new risk stratification based on clinical and histological severity. For classification, patients are divided into four groups (low, medium, high, and very high risk). However, differences in responsiveness to each treatment among different groups remain unclear. We evaluate the responsiveness of tonsillectomy plus steroid pulse (TSP) therapy using the new risk stratification. METHODS: We retrospectively reviewed 111 IgAN patients with TSP therapy between January 2003 and January 2013. Study patients were divided into three groups [low- (n = 40), medium- (n = 43) and high-/very high-risk group (n = 28)]. The primary outcome was clinical remission (CR). The observation period was 1 year following tonsillectomy. RESULTS: 57 out of 111 patients (51.4 %) reached CR. The CR incidence was 70.0, 41.9 and 39.3 % (the low-, the medium- and the high-/very high-risk group, respectively). The incidence of CR was significantly higher in the low-risk group (P = 0.013). In a multivariate logistic regression analysis, both the medium- and the high-/very high-risk group showed significantly lower incidence of inducing CR than the low-risk group [(odds ratio 0.324; 95 % confidence interval 0.106-0.939, P = 0.041) (odds ratio 0.239; 95 % confidence interval 0.058-0.910, P = 0.040), respectively]. CONCLUSIONS: The new risk stratification in the 2011 JSN clinical guidelines for IgAN had a positive impact on early CR of TSP therapy.

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.

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.

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.

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.

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.

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.