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Abstract Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR.

Abstract Background In Japan dialyzers are classified as type I, II, III, IV, or V on the basis of the β 2-microglobulin clearance. In 2023, Type V dialyzers were defined as super high-flux membrane dialyzers. Herein, we investigate the association between dialyzer type and mortality. Methods A cohort study was conducted using the Japanese Society for Dialysis Therapy Renal Data Registry database from 31 December 2017, to 31 December 2019. We enrolled 181,879 patients on hemodialysis who were divided into type I–V groups per the Japanese classification. We assessed the associations of each group with 2-year all-cause mortality using Cox proportional hazard models. Furthermore, propensity score matching analysis was performed. Results By the end of 2019, 34,196 patients (18.8%) had died. The hazard ratio (95% confidence interval) was significantly higher in the type I (1.25 [1.12–1.39]), type II (1.21 [1.13–1.31]), and type III (1.07 [1.02–1.13]) groups and significantly lower in the type V group (0.86 [0.80–0.92] P

Abstract Dialyzers are classified into five types based on their β2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a β2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis. Trial registration number: UMIN000018641

Abstract We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group’s change (P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage (P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: −32.3% [95% CI: −49.2%, −9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.

Abstract Background The 2020 Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) annual survey was sent to 4493 dialysis facilities in Japan. Methods Questionnaires were sent to all facilities that provide patients with dialysis therapy in Japan. Data were collected and compiled to form cross-sectional results of renal replacement therapy from various aspects. Results In total, 4437 facilities (98.8%) responded to the facility questionnaire and 4271 (95.1%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year, reaching 347,671 at the end of 2020 and giving a prevalence rate of 2754 patients per million population. The mean age was 69.40 years. Diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.5%), followed by chronic glomerulonephritis (25.3%) and nephrosclerosis (12.1%). There were 40,744 incident dialysis patients during 2020, representing a decrease of 141 from 2019. The average age of patients on dialysis was 70.88 years, with diabetic nephropathy being the most common underlying disease (40.7%) second most common was nephrosclerosis (17.5%), which was unchanged from the previous year and surpassed chronic glomerulonephritis (15.0%). There were 34,414 patient deaths in 2020; the crude mortality rate was 9.9%. The main causes of death were heart failure (22.4%), infection (21.5%), and malignancy (9.0%), which were almost the same as the percentages for the previous year. Since 2012, the number of patients treated by hemodiafiltration has increased rapidly; in 2020, the number of patients on this modality was 163,825, accounting for 47.1% of all patients on maintenance dialysis. The number of patients on peritoneal dialysis has been on the rise since 2017, reaching 10,338 in 2020; 20.8% of whom received combined therapy with hemodialysis or hemodiafiltration, showing no change from the previous year. A total of 751 patients were on home hemodialysis at the end of 2020, representing a decrease of 9 from the end of 2018. In 2020, coronavirus disease 2019 (COVID-19) infection and malignancy were added as new items in the survey. Continuing on from the 2019 survey, history of kidney donation for a living-donor transplant was investigated. Conclusions Present issues and challenges in renal replacement therapy were identified in the responses to the new questionnaire items included in this survey. A more detailed evaluation with adjustment for patient background factors should clarify the characteristics of the underlying diseases and conditions in dialysis patients. Trial registration The JRDR was approved by the Japanese Society for Dialysis Therapy ethics committee. It was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry on 10 September 2020 and in the UMIN clinical trials registration system (UMIN000018641).

Abstract A new marker reflecting the pathophysiology of chronic kidney disease (CKD) has been desired for its therapy. In this study, we developed a virtual space where data in medical words and those of actual CKD patients were unified by natural language processing and category theory. A virtual space of medical words was constructed from the CKD-related literature (n = 165,271) using Word2Vec, in which 106,612 words composed a network. The network satisfied vector calculations, and retained the meanings of medical words. The data of CKD patients of a cohort study for 3 years (n = 26,433) were transformed into the network as medical-word vectors. We let the relationship between vectors of patient data and the outcome (dialysis or death) be a marker (inner product). Then, the inner product accurately predicted the outcomes: C-statistics of 0.911 (95% CI 0.897, 0.924). Cox proportional hazards models showed that the risk of the outcomes in the high-inner-product group was 21.92 (95% CI 14.77, 32.51) times higher than that in the low-inner-product group. This study showed that CKD patients can be treated as a network of medical words that reflect the pathophysiological condition of CKD and the risks of CKD progression and mortality.

Abstract Background The Japanese Society for Dialysis Therapy is conducting the survey annually since 1968. The results provide a comprehensive picture of dialysis therapy in Japan. The survey for the year 2019 was performed as of December 2019. Methods Questionnaires were sent to all facilities that provide patients with dialysis therapy in Japan as an Excel file. Data were collected and compiled to form cross-sectional results of dialysis therapy from various aspects. Results At the end of 2019, the annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was conducted at 4487 dialysis facilities, of which 4411 facilities (98.3%) responded to the facility survey and 4238 facilities (94.5%) responded to the patient survey. The number of chronic dialysis patients in Japan continues to increase every year; it reached 344,640 at the end of 2019, and the prevalence ratio of dialysis patients was 2732 per million population. In the patient survey, the mean age of prevalent dialysis patients was 69.09 years. The most prevalent primary disease among prevalent dialysis patients was diabetic nephropathy (39.1%), followed by chronic glomerulonephritis (25.7%) and nephrosclerosis (11.1%). In 2019, there were 40,885 new patients on dialysis, an increase of 417 over 2018. The average age of incident dialysis patients was 70.42 years, and diabetic nephropathy (41.6%) was the most common cause. The second cause was nephrosclerosis, followed by glomerulonephritis. As 34,642 patients passed away in 2019, the crude mortality rate for the year was 10.1%. Heart failure (22.7%), infectious disease (21.5%), and malignancy (8.7%) were the three leading causes of death. Since 2012, the number of patients treated by hemodiafiltration (HDF) has increased substantially. The figure reached 144,686 by year's end, representing 42.0% of all dialysis patients. In 2019, the number of peritoneal dialysis (PD) patients was 9,920, a small rise from 2017. 19.2% of PD patients also received hemodialysis (HD) or HDF to compensate for the reduction in dialysis dosage or in fluid removal by PD alone (hybrid therapy). At the end of 2019, 760 patients received home HD therapy, an increase of 40 from 2018. In 2019, a detailed survey was conducted on the current status of CKD-MBD treatment, 10 years after the previous survey in 2009. The clinical efficacy of newly released medications during this time period and the impact of the 2012 revisions to the CKD-MBD guidelines require further investigation. These analyses would serve as the foundation for the next revision of the CKD-MBD guidelines and may reveal deeper therapeutic insights regarding CKD-MBD. Conclusions The results obtained by the survey revealed the comprehensive practice patterns of dialysis therapy and served as a basis for future guidelines. Trial registration: JRDR was approved by the ethics committee of JSDT (approval number 1–5) and registered in the "University hospital Medical Information Network (UMIN) Clinical Trials Registry" on 10th September 2019 with a clinical trial ID of UMIN000018641. https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000021578 (Accessed 20 November 2020).

Abstract Background The potential for developing frailty exists in middle‐aged and older adults. While obesity and metabolic syndrome (MetS) increase the risk of frailty in older adults, this relationship remains unclear in middle‐aged adults, who are prone to developing lifestyle‐related diseases. Objective To examine the effect of overweight/obesity and MetS on frailty development in middle‐aged and older Japanese adults using real‐world data. Methods This nationwide cohort study used exhaustive health insurance claims data of 3,958,708 Japanese people from 2015 to 2019 provided by the Japan Health Insurance Association. Participants aged ≥35 and

The objective of this study was to investigate the efficacy and safety of intradialytic parenteral nutrition (IDPN) using ENEFLUID® (310 kcal, 550 mL) in mild-moderate malnutrition patients receiving maintenance hemodialysis. A total of 40 adult patients with a Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) score of 5-10 were enrolled in this multicenter, randomized, open-label study. Patients in the intervention group received IDPN using ENEFLUID® via the dialysis circuit 3 times a week for 12 weeks; those in the control group did not. The primary endpoint was change in serum transthyretin (TTR). The secondary endpoints were changes in nutritional laboratory tests, nutritional parameters, food intake, plasma amino acids, and blood glucose. For both groups, mean age (72.1±11.4 years) and BMI (20.3±3.0), and median NRI-JH score [7.0 (interquartile range, 6-8)], did not differ. One patient withdrew before intervention, leaving 20 intervention and 19 control patients. Mean (95% confidence interval) change in serum TTR (mg/dL) at 12 weeks did not differ between groups: Intervention, 1.0 (-1.1-3.2); Control, -0.3 (-2.4-1.9); Intragroup difference, 1.3 (-1.7-4.3); P = 0.41. The values reflecting protein intake at 12 weeks compared to those on the study initiation day increased in the intervention group [the changes of blood urea nitrogen, 9.4 (2.6-16.2) mg/dL; P = 0.007, and normalized protein catabolic rate, 0.10 (0.02-0.18) g/kg/day; P = 0.02]. Mean food protein intake (g/kg/day) at 12 weeks increased in the intervention group and decreased in the control group, and differed between groups: Intervention, 0.12 (-0.03-0.28); Control, -0.18 (-0.43-0.08); Inter-group difference, 0.30 (0.00-0.60); P = 0.050. No adverse events occurred. In patients with mild to moderate malnutrition receiving ENEFLUID® for 12 weeks as IDPN, serum TTR was not improved, decreases in protein intake was mitigated, no adverse events occurred. Trial registration Name of the registry: Japan Registry of Clinical Trials Registration number: jRCTs031220296.

There are cases in which CKD progression is difficult to evaluate, because the changes in estimated glomerular filtration rate (eGFR) and proteinuria sometimes show opposite directions as CKD progresses. Indices and models that enable the easy and accurate risk prediction of end-stage-kidney disease (ESKD) are indispensable to CKD therapy. In this study, we investigated whether a CKD stage coordinate transformed into a vector field (CKD potential model) accurately predicts ESKD risk. Meta-analysis of large-scale cohort studies of CKD patients in PubMed was conducted to develop the model. The distance from CKD stage G2 A1 to a patient's data on eGFR and proteinuria was defined as r. We developed the CKD potential model on the basis of the data from the meta-analysis of three previous cohort studies: ESKD risk = exp(r). Then, the model was validated using data from a cohort study of CKD patients in Japan followed up for three years (n = 1,564). Moreover, the directional derivative of the model was developed as an index of CKD progression velocity. For ESKD prediction in three years, areas under the receiver operating characteristic curves (AUCs) were adjusted for baseline characteristics. Cox proportional hazards models with spline terms showed the exponential association between r and ESKD risk (p

Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). Results: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11). Conclusion: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

BackgroundInformation of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients.Materials and methodsWe analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study.ResultsUsing the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (pConclusionWe developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.

Hyperkalemia is associated with an increased risk of mortality and is a common complication in patients with chronic kidney disease (CKD). Despite the prevalence of hyperkalemia, current real-world data suggest that serum potassium levels are not effectively managed in clinical practice. The potential benefit of potassium binders in reducing the risk of death has not been thoroughly investigated. Therefore, this retrospective cohort study aimed to investigate the potential impact of potassium binders on mortality risk in patients with CKD by analyzing electronic medical records. The study included 1689 patients with CKD and hyperkalemia (serum potassium level > 5.0 mEq/L), who visited Kawasaki Medical School Hospital between January 2014 and December 2018. The patients were divided into two groups: those without CPS (calcium polystyrene sulphonate) treatment (CPS_OFF) and those with CPS treatment (CPS_ON). The results showed that the incidence of death was significantly higher in the CPS_OFF group than in the CPS_ON group (22.3% vs. 19.6%, p < 0.001). After propensity score matching, the CPS_ON group had a higher survival rate than the CPS_OFF group (log-rank test, p = 0.020). These results suggest that potassium binders may reduce the risk of death in patients with CKD and hyperkalemia. We hope that the results of this cohort study will be confirmed in future RCTs.

IntroductionChronic subdural hematoma (CSDH) is commonly treated using simple burr hole surgery. However, postoperative recurrence occurs at a relatively high rate of 10–20%. A decrease in platelet count (PC) may be associated with recurrence via a hemostasis disorder; however, this association has not been well-studied. Therefore, this study aimed to investigate the association between PC and postoperative CSDH recurrence.MethodsWe retrospectively reviewed the data for CSDHs in 488 cerebral hemispheres of 431 patients who underwent burr hole surgery at our institution between January 2013 and December 2022. The association between preoperative PC and postoperative CSDH recurrence was investigated. We used the first quartile of PC, PC

Abstract Background Hyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD. Methods This observational study utilized data from hospital records, claims, and health registers from the US (Optum’s de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode. Results A total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p

Abstract Chronic kidney disease (CKD) and heart failure (HF) are the first and most frequent comorbidities associated with mortality risks in early-stage type 2 diabetes mellitus (T2DM). However, efficient screening and risk assessment strategies for identifying T2DM patients at high risk of developing CKD and/or HF (CKD/HF) remains to be established. This study aimed to generate a novel machine learning (ML) model to predict the risk of developing CKD/HF in early-stage T2DM patients. The models were derived from a retrospective cohort of 217,054 T2DM patients without a history of cardiovascular and renal diseases extracted from a Japanese claims database. Among algorithms used for the ML, extreme gradient boosting exhibited the best performance for CKD/HF diagnosis and hospitalization after internal validation and was further validated using another dataset including 16,822 patients. In the external validation, 5-years prediction area under the receiver operating characteristic curves for CKD/HF diagnosis and hospitalization were 0.718 and 0.837, respectively. In Kaplan–Meier curves analysis, patients predicted to be at high risk showed significant increase in CKD/HF diagnosis and hospitalization compared with those at low risk. Thus, the developed model predicted the risk of developing CKD/HF in T2DM patients with reasonable probability in the external validation cohort. Clinical approach identifying T2DM at high risk of developing CKD/HF using ML models may contribute to improved prognosis by promoting early diagnosis and intervention.

Introduction: Hyperkalemia (HK) is a common disorder in patients with heart failure or chronic kidney disease, and potassium binders (PBs) are recommended to control serum potassium (S-K) levels. Although HK is often a chronic condition, short-term and intermittent PBs treatment has been largely applied to control S-K levels, and little is known about the impact of long-term and chronic PBs treatment on clinical outcomes.Method: This retrospective cohort study was conducted using a Japanese claims database (April 2008–September 2018). HK was defined as at least two S-K ≥5.1 mmol/L within a 12-month(M) interval. The index date was defined as the initial PB prescription date, and the S-K values were examined at 3M, 6M, and 12M after the index. The medication possession ratio (MPR) was used to evaluate the length of the prescribed period of PB, as prescription refill was not allowed in Japan. Clinical outcomes were analyzed by comparing MPR

Abstract Aims Cardiac troponin (cTn) and B‐type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD‐induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in 0.04 ng/mL) with a median (inter‐quartile range) level of 0.020 (0.005–0.041) ng/mL, and 1140 (99%) patients had elevated NT‐proBNP (cut‐off for heart failure: >125 pg/mL) with a median level of 3658 (1689–9356) pg/mL. There were 167 deaths during a median follow‐up of 2.8 (2.2–2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was 0.04 ng/mL (vs. cTnI 8000 pg/mL (vs. NT‐proBNP

Although the economic burden of multimorbidity is a growing global challenge, the contribution of multimorbidity in patients with high medical expenses remains unclear. We aimed to clarify multimorbidity patterns that have a large impact on medical costs in the Japanese population. We conducted a cross-sectional study using health insurance claims data provided by the Japan Health Insurance Association. Latent class analysis (LCA) was used to identify multimorbidity patterns in 1,698,902 patients who had the top 10% of total medical costs in 2015. The present parameters of the LCA model included 68 disease labels that were frequent among this population. Moreover, subgroup analysis was performed using a generalized linear model (GLM) to assess the factors influencing annual medical cost and 5-year mortality. As a result of obtaining 30 latent classes, the kidney disease class required the most expensive cost per capita, while the highest portion (28.6%) of the total medical cost was spent on metabolic syndrome (MetS) classes, which were characterized by hypertension, dyslipidemia, and type 2 diabetes. GLM applied to patients with MetS classes showed that cardiovascular diseases or complex conditions, including malignancies, were powerful determinants of medical cost and mortality. MetS was classified into 7 classes based on real-world data and accounts for a large portion of the total medical costs. MetS classes with cardiovascular diseases or complex conditions, including malignancies, have a significant impact on medical costs and mortality.

Chronic kidney disease (CKD) patients have high risks of end-stage kidney disease (ESKD) and pre-ESKD death. Therefore, accurately predicting these outcomes is useful among CKD patients, especially in those who are at high risk. Thus, we evaluated whether a machine-learning system can predict accurately these risks in CKD patients and attempted its application by developing a Web-based risk-prediction system. We developed 16 risk-prediction machine-learning models using Random Forest (RF), Gradient Boosting Decision Tree, and eXtreme Gradient Boosting with 22 variables or selected variables for the prediction of the primary outcome (ESKD or death) on the basis of repeatedly measured data of CKD patients (n = 3,714; repeatedly measured data, n = 66,981) in their electronic-medical records. The performances of the models were evaluated using data from a cohort study of CKD patients carried out over 3 years (n = 26,906). One RF model with 22 variables and another RF model with 8 variables of time-series data showed high accuracies of the prediction of the outcomes and were selected for use in a risk-prediction system. In the validation, the 22- and 8-variable RF models showed high C-statistics for the prediction of the outcomes: 0.932 (95% CI 0.916, 0.948) and 0.93 (0.915, 0.945), respectively. Cox proportional hazards models using splines showed a highly significant relationship between the high probability and high risk of an outcome (p

Abstract Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β2-microglobulin clearance rates of

Objective: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease. Patients and Methods: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score–matched hyperkalemic patients and normokalemic controls. Results: Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was −5.75 and −1.79 mL/min/1.73 m2, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively. Conclusion: Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.

Background: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease. Methods: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models. Results: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05–1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01–1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05–1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137–140 mEq/L) and the lowest ΔSNa (≤2 mEq/L). Conclusions: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.

Abstract The identification of malnutrition-inflammation-complex (MIC) and functional status (FS) is key to improving patient experience on hemodialysis (HD). We investigate the association of MIC and FS combinations with mortality in HD patients. We analyzed data from 5630 HD patients from 9 countries in DOPPS phases 4–5 (2009–2015) with a median follow-up of 23 [IQR 11, 31] months. MIC was defined as serum albumin 3 mg/L in Japan and > 10 mg/L elsewhere. FS score was defined as the sum of scores from the Katz Index of Independence in Activities of Daily Living and the Lawton-Brody Instrumental Activities of Daily Living Scale. We investigated the association between combinations of MIC (+/−) and FS (low [

BackgroundAppropriate maxillofacial growth and development evaluation is important for effective orthodontic treatment. Growth evaluation is based on physiological age determined by individual development, but not chronological age. One strategy for determining physiological age is using the cervical vertebral bone age.ObjectivesThis study aimed to clarify the standard size of the upper and lower jawbones in Japanese patients using the cervical vertebral maturation stages (CVMS) as an index and clarify the growth pattern. And to use the cervical spine age as a diagnostic aid in orthodontic treatment.Material and methodsRandom sampling was performed from the outpatients who visited the Orthodontics department, Tokyo Medical and Dental University Dental Hospital, and 400 patients were enrolled before treatment. Lateral cephalometric radiographs were obtained to measure the height and length of the mandible and the maxilla length with cephalometric analysis. Standard values were calculated for each cervical-spine-age group to analyze changes during mandibular and maxillary growth. Furthermore, we compared the differences between males and females. The Kruskal-Wallis test was used to compare cervical-spine-age groups, and the Steel-Dwass test was used for multiple comparisons. The reliability of CVMS was confirmed by calculating the weighted kappa coefficient (κ).Resultsκ for the degree of intra-evaluator agreement and the degree of the inter-evaluator agreement were calculated, and both indicated almost perfect agreement. We found that the distance between the anterior nasal spine (ANS) and posterior nasal spine (PNS) (i.e., ANS-PNS) increased significantly between CVMS II and CVMS III in males. The distance between Articulare (Ar) and Gonion (Go) (i.e., Ar-Go) and the distance between Go and Pogonion (Pog) (i.e., Go-Pog) increased significantly between CVMS III and CVMS IV in males.ConclusionThe findings suggested that CVMS is a reliable indicator of the growth stage of the maxilla and mandible.

Introduction: An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied. Methods: An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008–September 2017; N = 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed. Results: Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1–68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3–231.5), heart failure (134.0; 95% CI: 131.2–136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6–144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1–5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2–8.0). The 3-year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1–5.4, 5.5–5.9, and ≥6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K (≥5.1 mEq/l). Conclusion: This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds. Keywords: chronic kidney disease, congestive heart failure, hyperkalemia, renin-angiotensin-aldosterone inhibitor, renin angiotensin system

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.

Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152). The primary outcome was defined as end-stage kidney disease (ESKD) or death and was examined over a 1-year observation period. Overall, the mean Zn level was 59.6 μg/dl and the median eGFR was 20.3 ml/min/1.73 m2. The incidence of the primary outcome was higher in the low-Zn group (p

Rationale & Objective: Hyperkalemia is a common electrolyte abnormality of chronic kidney disease and heart failure associated with increased mortality and morbidity. We aimed to assess the long-term economic burden of hyperkalemia. Design: Observational cohort study using a Japanese nationwide hospital claims database (April 1, 2008, to September 30, 2018). Setting & Population: : Patients 18 years or older with at least 1 serum potassium value (N = 1,208,894). Exposures: Hyperkalemia defined with the presence of at least 2 serum potassium values ≥ 5.1 mmol/L. Outcome Measures: Direct health care costs and resource use in patients with hyperkalemia within and after 12 months from first hyperkalemia episodes. Analytical Approach: Health care costs and resource use were compared with propensity score–matched or nonmatched normokalemic controls. Multivariable regression analysis was performed to examine factors associated with health care costs. Results: 27,534 patients with hyperkalemia and 233,098 normokalemic controls were studied. Mean ± SD age was 73±13 years in patients with hyperkalemia; among them, 59% and 35% had chronic kidney disease and heart failure, respectively. In the propensity score–matched cohort (n = 5,859 in each group), average numbers of hospitalizations per patient per year in patients with hyperkalemia within and after 12 months were 1.2 and 1.6 times higher, respectively, compared with those in patients with normokalemia. The total cost per patient in patients with hyperkalemia was higher than for controls, with mean differences of $8,611 (95% CI, $8,046-$9,175) within 12 months and $5,150 (95% CI, $4,733-$5,566) after 12 months. The number of repeat hyperkalemic episodes was the factor with the strongest association with long-term health care costs, whereas severity of hyperkalemia was not associated. Limitations: This study used secondary data; therefore, residual confounders may not be fully excluded. Conclusions: Hyperkalemia was associated with significant long-term economic burden with frequent hospitalizations due to recurrent episodes, indicating the importance of hyperkalemia treatment for the sake of reducing health economic burdens and clinical complications.

Objective: To determine the phase that facilitates flap observation of the ascending aorta in Stanford type A acute aortic dissection with perfused false lumen. Methods: We reconstructed retrospective Electrocardiogram-gated Computed Tomography Angiography images of the ascending aorta of all 20 patients to 20 phases of curved-multiplanar reconstruction in 5% increment. One radiologist created and randomized 10 cross-sectional images of each phase for every patient and two radiologists scored these images on a 5-point scale depending on the degree of flap stoppage. We calculated the average score for each phase of each case and compared them among the three groups. Results: Image scores were significantly better in the 65 %–100 % R-R interval group than those in the 5%–30 % (p < 2e-16) and 35 %–60 % R-R interval groups(p = 7.2e-10). Similar scores were observed in the Heart Rate > 70 group (p = 0.00039, 2.2e-14). Moreover a similar tendency was observed in the arrhythmia group (p = 0.0035, 0.294). No difference was found in the degree of flap stoppage in the 65 %–100 % R-R interval group between the Heart Rate > 70 and Heart Rate ≤ 70 groups (p = 0.466) and between the arrhythmia and non-arrhythmia groups (p = 0.1240). Conclusion: In observing the ascending aorta, We obtained a good image at 65 %–100 % R-R interval and similar tendency was observed in the patients with arrhythmia.

BACKGROUND:Although dialysis patients are at a high risk of death, it is difficult for medical practitioners to simultaneously evaluate many inter-related risk factors. In this study, we evaluated the characteristics of hemodialysis patients using machine learning model, and its usefulness for screening hemodialysis patients at a high risk of one-year death using the nation-wide database of the Japanese Society for Dialysis Therapy. MATERIALS AND METHODS:The patients were separated into two datasets (n = 39,930, 39,930, respectively). We categorized hemodialysis patients in Japan into new clusters generated by the K-means clustering method using the development dataset. The association between a cluster and the risk of death was evaluated using multivariate Cox proportional hazards models. Then, we developed an ensemble model composed of the clusters and support vector machine models in the model development phase, and compared the accuracy of the prediction of mortality between the machine learning models in the model validation phase. RESULTS:Average age of the subjects was 65.7±12.2 years; 32.7% had diabetes mellitus. The five clusters clearly distinguished the groups on the basis of their characteristics: Cluster 1, young male, and chronic glomerulonephritis; Cluster 2, female, and chronic glomerulonephritis; Cluster 3, diabetes mellitus; Cluster 4, elderly and nephrosclerosis; Cluster 5, elderly and protein energy wasting. These clusters were associated with the risk of death; Cluster 5 compared with Cluster 1, hazard ratio 8.86 (95% CI 7.68, 10.21). The accuracy of the ensemble model for the prediction of 1-year death was 0.948 and higher than those of logistic regression model (0.938), support vector machine model (0.937), and deep learning model (0.936). CONCLUSIONS:The clusters clearly categorized patient on their characteristics, and reflected their prognosis. Our real-world-data-based machine learning system is applicable to identifying high-risk hemodialysis patients in clinical settings, and has a strong potential to guide treatments and improve their prognosis.

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.MethodsIn total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsLogistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.ConclusionsWe determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD.MethodsIn total, 31,082 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsThe mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09-2.58]), G4 (5.50 [4.80-6.31]), and G5 (9.75 [8.13-11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5.ConclusionsWe determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.

Abstract Background Low tongue pressure contributes to oral frailty. It is a condition in which the pressure between the tongue, palate, and food decreases due to a decrease in tongue muscle function. Low tongue pressure interferes with chewing and swallowing and causes bloating, increasing the risk of malnutrition and aspiration pneumonia due to decreased intake. Its causes include aging, neuromuscular disease, trauma, sequelae, low nutrition, and sarcopenia. Although quantitative evaluation of tongue function has been reported to be useful for prevention of low tongue pressure, there is no report of the evaluation’s effectiveness in patients with high-risk renal failure. This study aimed to evaluate the prevalence of low tongue pressure and to clarify the relationship between the tongue pressure value and sarcopenia in peritoneal dialysis (PD) patients. Methods A cross-sectional study of 105 PD patients (67 ± 13.5 years old, 73.3% men, 26.7% women; 26.7% with diabetes) was conducted in our hospital. At the start of the study, clinical backgrounds were investigated from the patients’ medical records. Sarcopenia was diagnosed by muscle mass, grip strength, and walking speed. Inflammatory, nutritional, and cardiovascular markers were measured. Univariate and multivariate analyses with muscle and nutrition markers were performed to determine the low tongue pressure prevalence rate in PD patients. Results Low tongue pressure prevalence rate was 55.2% in patients under 65 and 64.1% in patients 65 and over. Significantly lower tongue pressure (p = 0.019) was observed in the patients in the sarcopenic group. The tongue pressure value was positively correlated with albumin (p = 0.0003), pre-albumin (p = 0.006), body mass index (p = 0.004), grip strength (p

Background: Overt proteinuria (OP), an established risk factor for kidney and cardiovascular disease, is much prevalent in high and low body weight individuals. Objectives: However, it is equivocal whether trace proteinuria (TrP) is also associated with high and low body weight. Therefore, we address this issue in a large epidemiological study. Patients and Methods: Regarding this association, we examined TrP defined as ± by dipstick urinalysis, in comparison with OP (≥+1) using the data of 70 886 apparently healthy Japanese men and women who underwent a checkup in 2008, aged 20-85 years old. Results: The prevalence of TrP, which was slightly but significantly higher (4.1%) on average compared with OP (3.1%), showed a J-shaped relationship against body mass index (BMI). Logistic regression analysis showed that compared to BMI of 21.0-22.9 kg/m2 , other BMI categories except BMI of 19.0–20.9 kg/m2 were significantly associated with TrP, which were not altered after adjustment for relevant confounding factors including age, sex, and pharmacotherapies for hypertension and diabetes. Unlike TrP, OP was not significantly associated with BMI of 23.0–24.9 kg/m2 , a high-normal body weight, although similar trends were observed in the overall relationship between BMI categories and OP. Conclusions: Current study suggests that TrP is also associated with high and low body weight, seemingly like OP. However, the degree and pattern of associations of TrP with BMI may differ from those of OP. Further study is required particularly in terms of fundamental clinical relevance of TrP.

Abstract Objective Hearing loss may be associated with certain sleep abnormalities. We recently reported that subclinical hearing loss (SHL) was more prevalent in individuals in a broad Japanese population who slept longer than 8 h; however, the underlying mechanism was unknown. Therefore, we investigated the association between SHL and self-reported restorative sleep (RS), assessed by questionnaire, in a database of 33,888 Japanese aged 40–69 years without overt or diagnosed hearing loss (20,225 men, 13,663 women). Results The proportion of individuals with RS (more than half of the subjects) was significantly higher in the group with bilateral than with unilateral SHL at 4000 Hz and intact hearing; however, that was not the case at 1000 Hz, independent of age (P

Abstract Background Chronic kidney disease is a major risk factor for dementia, but the influence of hemodialysis itself on the development of dementia remains unclear. We previously reported that non-diabetic patients on maintenance hemodialysis have preserved cognitive function; hemodialysis removes blood amyloid β (Aβ), which is a major cause of Alzheimer’s disease in the brain; and the number of Aβ deposits in the postmortem brains of hemodialysis patients was significantly less compared to that in age-matched controls not undergoing hemodialysis. We aimed to evaluate the influence of hemodialysis on the development of dementia. Methods We accessed the Japanese Society for Dialysis Therapy Renal Data Registry between December 31, 2009, and December 31, 2010. Dementia was identified in 120,101 patients undergoing maintenance hemodialysis. The association between hemodialysis duration and dementia risk was analyzed using logistic regression analysis. Results There was a significant decrease in the dementia risk with an increase in the hemodialysis duration, with odds ratios (95% confidence intervals) of 0.78 (0.74–0.82) and 0.88 (0.78–0.99) for every 10 years in non-diabetic and diabetic patients, respectively. However, in diabetic patients, the correlation between hemodialysis duration and dementia risk was not consistent. Conclusion A longer hemodialysis duration was correlated with a lower dementia risk, but the correlation between hemodialysis duration and dementia risk in diabetic patients was much weaker and vaguer than that in non-diabetic patients. This finding does not appear to contradict greatly the assumption that the reduction in dementia risk with a prolonged hemodialysis duration in non-diabetic patients was caused not only by the survivor effect but also by hemodialysis itself.

Abstract Background The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman’s rank-correlation coefficient. Results Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change − 0.6 ± 0.7%, P

Abstract Background Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM. Methods DEFENCE is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial. Between October 2015 and August 2016, 80 T2DM patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0 and 7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P

Abstract Background The Scientific Academy Committee of Japanese Society for Dialysis Therapy (JSDT) has developed 14 clinical practice guidelines (CPGs) and their revised editions independently or in cooperation with other organizations and translated many of them into English to make them available to the world. These guidelines were presented in a user-friendly textbook-like format and were useful for many healthcare professionals engaged in dialysis therapy. However, because the definition and the process for developing CPGs have recently become more rigorous worldwide, the conventional process of development and the format of JSDT no longer meet the requirements for CPGs. Method Since 2012, JSDT, with its Guideline Developing Working Group (formerly Guideline Subcommittee), had evaluated several CPGs developing systems. The working group evaluated the advantages and disadvantages of several CPGs developing systems. The most important point of them which JSDT would adopt for their own system was to be based on evidence and be able to receive international recognition. Results In Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system, the quality of evidence was evaluated by systematic review on each clinical outcome by systematic review panel. After the report from the systematic review panel, the CPG panel grades the strength of recommendation on each CPG statement. GRADE system was the most frequently used for developing CPGs by many human healthcare societies in the world. If JSDT adopt GRADE system, it is necessary for us to learn how to assess the quality of evidence through a systematic review, to develop a system for determining the strength of recommendation on the basis of a systematic review, and to decide how to manage any conflicts of interest. Conclusions JSDT should provide the useful information from Japanese experiences on chronic dialysis to the world. In order to achieve this aim, we concluded that the most reasonable approach is to utilize the data from JSDT Renal Data Registry in a more creative manner, publish such data for the world as evidence, and develop CPGs in accordance with a globally recognized methodology, GRADE. Notification The current manuscript is the position statement of JSDT for developing future CPGs and the second publication of “Policy for Developing Clinical Practice Guidelines (CPGs) of the Japanese Society for Dialysis Therapy” on J Jpn Soc Dial Ther 2016; 49: 453-62 (in Japanese), with permission.

Introduction: Recently, the sodium-glucose cotransporter2 (SGLT2) inhibitor empagliflozin has been shown to lower cardiovascular risk among diabetic patients. It is intriguing that some SGLT2 inhibitors have been found to increase low-density lipoprotein (LDL) cholesterol levels, while the relevance to high-density lipoprotein (HDL) cholesterol is unknown. Although the inhibitory effect of SGLT2 inhibitors on glucose reabsorption may accelerate compensatory lipid metabolism and subsequently reduce body weight and affect the lipid profile, much remains unclear about this mechanism. Therefore, we conducted this study to investigate in detail how canagliflozin affects lipoprotein fractions including LDL and HDL subclasses. Materials and Methods: This study is a multicenter prospective study. The participants were patients with 22 type 2 diabetes (60.7 ± 11.6 years, 59.1% of men) who had HbA1c ⩾ 7.0% and consented to participate in the study. They were administered 100 mg canagliflozin orally once per day. Biochemistry test and cholesterol levels of 20 lipoprotein fractions (G1-G20) using high performance liquid chromatography methods were examined before and after 12 weeks of treatment period. Results: Significant decreases were observed in the participants’ body weight (69.7 to 67.9 kg, P < .001), systolic blood pressure (129.3 to 119.5 mm Hg, P < .01), and HbA1c (8.5% to 7.4%, P < .001). Cholesterol levels in the 20 lipoprotein fractions increased for very large HDL (G14, G15) and large HDL (G16) ( P < .05). Conclusions: Reduction in body weight, improvement of blood glucose levels, and increases in very large HDL and large HDL subclasses were observed after canagliflozin treatment. These beneficial changes might contribute to subsequent suppression of cardiovascular outcomes.

BACKGROUND:Protein energy wasting (PEW) is a risk factor for death. However, the cutoff vales for PEW are not optimized for early identification of hemodialysis patients with malnutrition. We evaluated the prognosis of Japanese maintenance hemodialysis patients using nutritional indices optimized for them. MATERIALS AND METHODS:We analyzed data from a nation-wide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry to develop and validate a nutritional risk index (n = 48349, 48349, respectively). The association of nutritional factors with one-year death was tested using Cox proportional hazards models. Their cutoff levels were determined from the hazard ratios or receiver operating characteristic curves. Then, risk index was developed using scoring models. RESULTS:Male was 61.4%; average age, 65.7±12.2 years; and diabetes mellitus, 32.8%. Four clinical factors were retained in the final model: low BMI (

In patients with chronic kidney disease (CKD), low body mass index (BMI) is associated with high mortality. This relationship in emergently hospitalized CKD patients is unknown. We investigated the association between obesity and short-term mortality in emergently admitted patients with dialysis-independent CKD (DI-CKD) with and without infection. This retrospective cohort study examined Diagnosis Procedure Combination data of 26103 emergently hospitalized DI-CKD patients. Patients were divided into 8 groups according to their BMI and the presence of infectious diseases. The primary outcome was in-hospital death within 100 days. Cox proportional hazards models adjusted for baseline characteristics showed that low BMI was associated with the outcome both in infected and in non-infected patients (reference group as non-infected and medium BMI [24-26 kg/m2] group): infected and the lowest BMI (≤20 kg/m2) group, hazard ratio (HR) 1.82 (95% confidence interval 1.51, 2.19); non-infected and the lowest BMI group, 1.39 (1.16, 1.67). When patients were stratified according to presence of diabetes mellitus (DM), patients with DM showed that low BMI was associated with the outcome both in infected and in non-infected patients, whereas in non-DM patients, this relationship was attenuated in the non-infected group. For emergently hospitalized CKD patients with infection, high BMI was associated with lower mortality irrespective of the DM status. For non-infected patients, the effects of obesity for in-hospital mortality were modified by the DM status.

Atherosclerosis is often a complication of chronic kidney disease (CKD) because of dyslipidemia and CKD-mineral and bone disorder. High-density lipoproteins (HDLs) are grouped into various subclasses composed of multiple proteins and lipids, and their transformation is altered in CKD. We investigated the roles of lipoprotein subclasses in CKD progression, and atherosclerosis, and the relationships with Klotho and fibroblast growth factor (FGF) 23.Seventy-one CKD patients were enrolled in this prospective cohort study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) and lipoprotein particle numbers in 20 lipoprotein fractions were measured by a newly developed high-performance gel permeation chromatography.Diabetic nephropathy was observed in 23.9% of the patients. The mean age was 75.0 years and estimated glomerular filtration rate (eGFR) was 17.2 ml/min./1.73m2. The lipoprotein particle numbers in small HDLs were higher in Stage 4 group than in Stage 5 group (p = 0.002). Multivariate regression analysis adjusted for baseline characteristics showed that the cholesterol proportions in very small HDLs were associated with eGFR change rate [F19 β = -17.63, p = 0.036] and ABI [F19 β = 0.047, p = 0.047] in Stage 4 group, and that serum soluble α-Klotho level was associated with the lipoprotein particle numbers in very small HDLs [F19 β = 0.00026, p = 0.012; F20 β = 0.00041, p = 0.036] in Stage 5 group.This study showed that HDL subclasses are associated with CKD progression, ABI, and Klotho level in CKD-stage-specific manner.

For hemodialysis (HD) patients, many risk factors for death are associated with each other intricately. However, they are often considered separately in clinical settings. We evaluated the maintenance HD patients' risk of death within one year from multiple risk factors simultaneously considering their interrelationships using a novel index (survival index, SI) for HD patients in the United States developed using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS).We analyzed data from 3899 and 3765 patients to develop and validate SI, respectively. To predict death within one year, candidate models were developed using logistic regression models. The final model was determined by comparing the accuracy among the models for the prediction of deaths.The model included age; body mass index; serum creatinine, albumin, total cholesterol and phosphorus levels; history of cardiovascular diseases; and arteriovenous fistula use. SI showed a higher accuracy in predicting death (c-statistic, 0.739) than geriatric nutritional risk index (0.647) and serum albumin level (0.637). The probability of death predicted on the basis of SI matched the observed number of deaths. Cox proportional hazard models for time-dependent SI showed that patients with low SI had a higher risk of death than patients with high SI [reference, Group 4 (26.1≤SI)]; Group 1 (SI

BACKGROUND:The relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people. MATERIALS AND METHODS:Healthy people were enrolled in this community-based prospective cohort study, the Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. The analysis was conducted on 4188 subjects followed up for at least 3 years, 3102 for 6 years and 1052 for 9 years. Their data including glomerular filtration rate (eGFR) decline were examined every three years. The outcome event was incident CKD or the decrease in eGFR by more than 25% in three years. Multivariate statistical models were adjusted for the baseline characteristics. RESULTS:The following data was obtained: mean ± SD age, male, 39.6 ± 10.4 years, female 38.4 ± 10.8 years; eGFR, male, 81.9 ± 16.4 ml/min/1.73 m2, female, 82.1 ± 17.5 ml/min/1.73 m2; serum uric acid level, male, 5.8 ± 1.2 mg/dl, female, 4.1 ± 0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male,

Obesity is associated with diabetes mellitus and cardiovascular diseases. However, it has been reported that weight loss is associated with incident chronic kidney disease (CKD) in healthy males. The purpose of this prospective cohort study is to investigate the effects of weight loss on kidney function in healthy people in terms of body mass index (BMI) and gender.A total of 8447 nondiabetic healthy people were enrolled in the Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. Relationships between estimated glomerular filtration rate (eGFR) change, BMI, and BMI change were evaluated using 3D-scatter plots with spline and generalized additive models (GAMs) adjusted for baseline characteristics.The subjects were stratified into four groups according to BMI. The mean±standard deviations for males and females were, respectively, 40.11±9.49, and 40.3±9.71 years for age and 76.39±17.72 and 71.49±18.4 ml/min/1.73m2 for eGFR. GAMs showed that a decreasing BMI change (

Although lifestyle is associated with metabolic syndrome and cardiovascular diseases, there has been no sufficient evidence of lifestyles on incident chronic kidney disease (CKD). The purpose of this prospective cohort study is to investigate the effects of lifestyles on kidney function in healthy people.A total of 7473 healthy people were enrolled in this Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. Data on alcohol consumption, exercise frequency, and sleep duration were collected. The outcome event was incident CKD or decrease in estimated glomerular filtration rate (eGFR) by >25% in 3 years.Subjects were classified into four groups according to body mass index and gender. Mean ± standard deviation of age was 38.8±10.5 years; eGFR, 78.1±15.2 ml/min/1.73 m2. In the male groups, multivariate logistic regression models showed that the outcome events were associated with a small amount of alcohol consumed (20 to 140 g of alcohol/week) (ref. more than 140 g of alcohol/week); non-obese male, adjusted odds ratio 1.366 (95% confidence interval, 1.086, 1.718); obese male (body mass index ≥25), 1.634 (1.160, 2.302); and with frequent exercise (twice a week or more) (ref. no exercise); non-obese male, 1.417 (1.144, 1.754); obese male, 1.842 (1.317, 2.577). Sleep duration was not associated with the outcome events.These findings suggest that, regardless of obesity, a small amount of alcohol consumed and high exercise frequency were associated with the increased risk of loss of kidney function in the male groups.