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Immobilization osteoporosis is characterized by excess bone resorption. Vitamin D receptor activators (VDRA) might have adverse effects in immobilized patients. The objective of this study was to elucidate the impact of performance status (PS) on the associations between VDRA use and outcomes among hemodialysis patients. This is a prospective cohort study. Adults on hemodialysis in the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry were included. Exposure of interest was the use of VDRA. Outcomes were all-cause mortality and hip fracture. Associations between VDRA use and mortality or hip fractures were examined by Cox and Poisson regression analyses, respectively. Among 208,512 subjects, 128,535 were on VDRA. Poor PS was associated with higher calcium (Ca), lower parathyroid hormone, and higher alkaline phosphatase levels. The association between higher Ca levels and VDRA use was stronger among those with poor PS (p interaction 0.007). Adjusted hazard ratio (HR) (95% confidence interval [CI]) for mortality and incidence rate ratio (IRR) for hip fracture was 1.02 (95% CI, 0.99-1.05) and 0.93 (0.86-1.00) among users of VDRA, respectively. The VDRA use was associated with lower mortality and incidence of hip fractures among subjects with good PS but not among subjects with poor PS (p interaction 0.03 and 0.05). Effect modification by PS was observed for cardiovascular (CV) mortality but not for non-CV mortality. In conclusion, VDRA use was associated with better outcomes only among those with good PS. These results suggest that bone and mineral disorders among hemodialysis patients should be treated differently, depending on their performance status. © 2022 American Society for Bone and Mineral Research (ASBMR).

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 in2% of HD patients in real-world practice. This study aimed to examine whether routinely measured N-terminal pro-BNP (NT-proBNP) and cTnI (contemporary assay) are more appropriate than clinical models for reclassifying the risk of HD patients who have the highest risk of death.Pre-dialysis levels of cTnI and NT-proBNP at study enrolment were measured in 1152 HD patients (Japan DOPPS Phase 5). The patients were prospectively followed for 3 years. Cox regression was used to test the associations of cardiac biomarkers with all-cause mortality, adjusting for potential confounders. Subgroup analyses were performed to assess potential effect modification of clinical characteristics, such as age, systolic blood pressure, HD vintage, diabetes mellitus, coronary artery disease, and a history of congestive heart failure. At baseline, 337 (29%) patients had elevated cTnI (99th percentile of a healthy population: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 was0.01 for both biomarkers. However, the prognostic significance of NT-proBNP was moderately diminished when cTnI was added to the model. The hazard ratios of mortality for cTnI 0.04 ng/mL (vs. cTnI 0.006 ng/mL) and NT-proBNP 8000 pg/mL (vs. NT-proBNP 2000 pg/mL) were 2.56 (95% confidence interval: 1.37-4.81) and 1.90 (95% confidence interval: 0.95-3.79), respectively. Subgroup analyses showed that the associations of both cardiac biomarkers with mortality were generally consistent between stratified groups.Routinely measured NT-proBNP and cTnI levels are strongly associated with mortality among prevalent HD patients. These associations remain robust, even after adjustment for alternative biomarkers, suggesting that cTnI and NT-proBNP have identical prognostic significance and may reflect different pathological aspects of cardiac abnormalities.

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.

The prevalence and severity of anemia differ between diabetic and non-diabetic patients. We investigated whether the effect of hemoglobin (Hb) on patient outcome was affected by the presence or absence of diabetes among Japanese patients receiving chronic hemodialysis (HD). We enrolled 149,308 patients from a nationwide dialysis registry in Japan at the end of 2012 (mean age, 67.6 ± 12.3 years; male, 61.7%; diabetes, 43.5%; median dialysis duration, 65 months) who underwent three HD sessions weekly. One-year all-cause and cardiovascular (CV) mortality were assessed using Cox regression analysis and competing-risks regression analysis. We used multiple imputation to deal with missing covariate data. Baseline Hb and serum ferritin levels were independently associated with all-cause and CV mortality. In non-diabetic patients, a significantly higher risk for all-cause mortality compared to the reference group (10 to 11 g/dL) was observed in patients with Hb

The appropriate protein intake for patients on hemodialysis complicated with frailty remains highly controversial.We conducted a prospective cohort study using data from Japanese Dialysis Outcomes and Practice Pattern Study. The patients were separated by their baseline of normalized protein catabolic rate (nPCR) into 3 categories: low (nPCR 1.0), medium (1.0 ≤ nPCR1.2), and high (nPCR ≥1.2). The frailty score was calculated based on the 12-item Short Form, and frailty was defined in cases with a total score of ≥2 points. The all-cause mortality was compared between groups using a Cox proportional hazard model.A total of 2,404 patients were included in the longitudinal analysis, 1,096 (45.6%) of whom had frailty. Patients in the low-nPCR group showed a higher prevalence of frailty than those in the other groups. In the Cox proportional hazard model, no significant differences in the all-cause mortality were noted between the low-nPCR and medium-nPCR groups or the high-nPCR and medium-nPCR groups. Furthermore, no significant differences were noted among any groups when subjects were limited to patients with frailty.Patients with a low nPCR have a higher prevalence of frailty and incidence of mortality than those with a medium nPCR. Patients with a high nPCR did not show a lower survival rate than those with a medium nPCR in this study. To clarify the appropriate protein intake for patients on hemodialysis with frailty, an intervention study or large-scale, long-term cohort study will be needed.

Blood pressure (BP) is reportedly a predictor of mortality in hemodialysis (HD) patients; however, it is unclear whether pre- or postdialysis BP has greater predictive power. To evaluate the association of pre- and postdialysis BP with patient survival in Japanese HD patients, we enrolled the entire phase 3 and 4 Japan Dialysis Outcomes and Practice Patterns Study populations. Among 3176 patients, 486 were excluded because of missing data. The remaining 2690 patients were divided into five groups according to pre- or postdialysis systolic BP (SBP)

Emerging data have demonstrated that sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent cardiovascular events, especially heart failure-associated endpoints. Cardiovascular outcome trials have also suggested their renoprotective effects. One large clinical trial investigated renal primary endpoints and demonstrated that SGLT2 inhibitors slowed the progression of diabetic kidney disease (DKD). This review summarizes clinical trial data on renal outcomes and discusses potential underlying mechanisms.The EMPA-REG, CANVAS, and DECLARE-TIMI 58 studies revealed that SGLT2 inhibitors reduce the risk of cardiovascular events and concomitantly suggested that these drugs slow the progression of kidney disease in type 2 diabetes. The CREDENCE trial on patients with high-risk type 2 diabetes and chronic kidney disease demonstrated that canagliflozin treatment reduced the relative risk of a composite outcome, including end-stage kidney disease, serum creatinine doubling, and renal/cardiovascular death, by 30% in these patients. Animal experiments revealed that oxidative stress, inflammation, fibrosis, and tubuloglomerular feedback are underlying renoprotective mechanisms behind SGLT2 inhibitors.Recent clinical trials have established the renoprotective effects of SGLT2 inhibitors. Further investigations on mechanisms of these renoprotective effects will provide deeper insights and understanding of pathogenetic properties of DKD.

Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 μg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 μg/ml and ≥ 6 μg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 μg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65–98.77; p = 0.02) or ≥ 6 μg/ml (OR, 18.33; 95% CI, 2.32–144.82; p = 0.006) were independent predictors of PR. This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition. We developed risk prediction models using extreme gradient boosting (XGB), multiple logistic regression (LR), and deep neural network. Models were derived from a retrospective cohort of hyperkalemic patients with either heart failure or chronic kidney disease stage ≥3a from a Japanese nationwide database (1 April 2008–30 September 2018). Studied outcomes included all-cause death, renal replacement therapy introduction (RRT), hospitalization for heart failure (HHF), and cardiovascular events within three years after hyperkalemic episodes. The best performing model was further validated using an external cohort. A total of 24,949 adult hyperkalemic patients were selected for model derivation and internal validation. A total of 1452 deaths (16.6%), 887 RRT (10.1%), 1,345 HHF (15.4%), and 621 cardiovascular events (7.1%) were observed. XGB outperformed other models. The area under receiver operator characteristic curves (AUROCs) of XGB vs. LR (95% CIs) for death, RRT, HHF, and cardiovascular events were 0.823 (0.805–0.841) vs. 0.809 (0.791–0.828), 0.957 (0.947–0.967) vs. 0.947 (0.936–0.959), 0.863 (0.846–0.880) vs. 0.838 (0.820–0.856), and 0.809 (0.784–0.834) vs. 0.798 (0.772–0.823), respectively. In the external dataset including 86,279 patients, AUROCs (95% CIs) for XGB were: death, 0.747 (0.742–0.753); RRT, 0.888 (0.882–0.894); HHF, 0.673 (0.666–0.679); and cardiovascular events, 0.585 (0.578–0.591). Kaplan–Meier curves of the high-risk predicted group showed a statistically significant difference from that of the low-risk predicted groups for all outcomes (p < 0.005; log-rank test). These findings suggest possible use of machine learning models for real-world risk assessment as a guide for observation and/or treatment decision making that may potentially lead to improved outcomes in hyperkalemic patients while retaining the benefit of life-saving therapies.

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 2-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.

OBJECTIVE Randomized controlled trials have shown kidney-protective effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown. RESEARCH DESIGN AND METHODS Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. RESULTS At baseline, mean age at initiation of the SGLT2 inhibitor (n = 1,033) or other glucose-lowering drug (n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m2, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m2 per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26–0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (Pheterogeneity ≥ 0.35). CONCLUSIONS The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.

Aims: Prediabetes and diabetes are associated with increased insulin resistance and decreased insulin production, dyslipidemia, and increased cardiovascular disease (CVD) risk. Our goals were to assess lipoprotein subfractions using novel assays in such subjects. Methods: Fasting normal, prediabetic, and diabetic Taiwanese men and women (n = 2,049) had their serum glucose, glycosylated hemoglobin, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, apolipoprotein E-HDL-C, direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-TG, and remnant lipoprotein cholesterol (RLP-C) levels measured using novel assays. HDL2-C, LDL-C, and large-buoyant LDL-C (lbLDL-C) were calculated. Results: Prediabetic male and female subjects had significantly higher levels of TG, RLP-C, sdLDL-C, the sdLDL-C/LDL-C ratio, and LDL-TG than normal subjects, and statin treatment abolished this effect in men, but not in women. Diabetic male and female subjects had significantly higher TG and sdLDL-C/LDL-C ratios, and significantly lower levels of HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, as did prediabetic women. Median direct LDL-C levels were > 100 mg/dL in all groups, even in those receiving statin therapy. Calculated LDL-C significantly underestimated direct LDL-C by > 10% in diabetic subjects. Conclusions: Our data indicate that prediabetic subjects were more likely to have significantly elevated RLP-C, sdLDL-C, and LDL-TG, while diabetic subjects were more likely to have significantly decreased HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, and calculated LDL-C significantly underestimated their direct LDL-C. In our view, direct LDL-C and sdLDL-C should be measured and optimized in both diabetic and prediabetic subjects to reduce CVD risk.

Lymphoid tissues, such as adenoids (Ad) and tonsils (Tn), are suggested to undergo hypertrophy during childhood and involution in adulthood. Enlargement of Ad and Tn can cause transient obstruction of the respiratory airways, thus inducing obstructive sleep apnoea. To date, the standard Ad and Tn sizes have not been reported, and there are no explicit objective criteria for evaluating their sizes or deducing whether they have enlarged, reduced, or remained constant over time. Our previous cross-sectional study revealed the age-dependent airway occupation ratio of Ad and Tn in Japanese individuals. We conducted a longitudinal observational study of the Ad and Tn sizes in Japanese individuals aged 6–20 years. Ninety individuals were retrospectively enrolled. The average and standard deviation of the sizes was calculated in 5 age-based groups.

Background It is known that sarcopenia is related to malnutrition-inflammation-atherosclerosis (MIA) syndrome and is an important problem in dialysis patients. The notion of frailty includes various physical, psychological, and social aspects. Although it has been reported that sarcopenia is associated with poor prognosis in patients with hemodialysis, reports on peritoneal dialysis (PD) patients are rare. In this study, we examined the morbidity and mortality of sarcopenia and frailty in PD patients. We also investigated the MIA-related factors. Methods We evaluated 119 patients cross-sectionally and longitudinally. The Asian Working Group for Sarcopenia criteria and the Clinical Frailty Scale (CFS) were used to diagnose sarcopenia and frailty. The primary outcome is all-cause mortality with sarcopenia and frailty. The secondary outcome is the relationship between various MIA-related factors. Results Morbidity of sarcopenia and frailty in PD patients was 8.4% and 10.9%, respectively. Old age, high values of Barthel Index, Charlson Comorbidity Index, CFS, and low values of body mass index (BMI), muscle strength, muscle mass, and slow walking were associated with sarcopenia. Interleukin-6, albumin, and prealbumin were significantly correlated with muscle mass. During follow-up, the presence of sarcopenia or frailty was associated with the risk of mortality. In multivariate analysis, CFS was related to the mortality rate of PD patients. Conclusions The presence of sarcopenia or frailty was associated with a worse prognosis.

Patients receiving dialysis therapy often have frailty, protein energy wasting, and sarcopenia. However, medical staff in Japan, except for registered dietitians, do not receive training in nutritional management at school or on the job. Moreover, registered dietitians work separately from patients and medical staff even inside a hospital, and there are many medical institutions that do not have registered dietitians. In such institutions, medical staff are required to manage patients’ nutritional disorders without assistance from a specialist. Recent studies have shown that salt intake should not be restricted under conditions of low nutrition in frail subjects or those undergoing dialysis, and protein consumption should be targeted at 0.9 to 1.2 g/kg/day. The Japanese Society of Dialysis Therapy suggests that the Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) is a useful tool to screen for older patients with malnutrition.

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 [

Background Appropriate 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. Objectives This 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 methods Random 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). Results κ 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. Conclusion The findings suggested that CVMS is a reliable indicator of the growth stage of the maxilla and mandible.

Aims: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C). Methods: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking. Results: In both men and women, current smokers had significantly ( p ＜0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly ( p ＜0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly ( p ＜0.05) more likely to have TG values ＞150 mg/dL (+56.8%, +116.3%), sdLDL-C ＞40.1 mg/dL (+28.8%, +44.9%), and HDL-C ＜40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships. Conclusion: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate 2 base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39,121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m2) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1,001 (2.6%), 2,612 (6.7%), 23,333 (59.6%), 8,357 (21.4%), 2,710 (6.9%) and 1,108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care.

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.

Context Angiopoietin-like protein 2 (ANGPTL2) is a circulating, proinflammatory protein. Objective To examine the role of ANGPTL2 in the pathogenesis of diabetic kidney disease (DKD), we studied the epigenetic regulation of angptl2 expression in patients with diabetes. Design, setting, participants, and intervention We determined the relationship between serum ANGPTL2 levels and the progression of DKD in cross-sectional (220 patients) and cohort (145 patients, 7-year follow-up) studies. Furthermore, we investigated the direct effect of ANGPTL2 on podocyte function. Main outcomes The main outcome was progression of DKD. Results We found that the expression of angptl2 was decreased by the methylation of its promoter region. Multivariate logistic regression analyses revealed that the baseline level of serum ANGPTL2 was an independent risk factor for the progression of DKD during follow-up periods. In cultured podocytes, ANGPTL2 directly increased albumin permeability through the translocation of zonula occludens-1 from the membrane to the cytosol via activation of focal adhesion kinase. Conclusions ANGPTL2 might be directly involved in podocyte dysfunction and independently associated with the progression of DKD stages.

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.

BACKGROUND Atrial fibrillation (AF) can be initiated from arrhythmogenic foci within the muscular sleeves that extend not only into the pulmonary veins but also into both vena cavae. The superior vena cava (SVC) is a key target site for catheter ablation. Patients with SVC-derived AF often lack the clinical risk factors of AF.Methods and Results:We conducted a meta-analysis of the clinical and genetic factors of 2,170 AF patients with and without SVC arrhythmogenicity. In agreement with previous reports, the left atrial diameter was smaller in AF patients with SVC arrhythmogenicity. Among 6 variants identified in a previous genome-wide association study in Japanese patients, rs2634073 and rs6584555 were associated with SVC arrhythmogenicity. This finding was confirmed in our meta-analysis using independent cohorts. We also found that SVC arrhythmogenicity was conditionally dependent on age, body mass index, and left ventricular ejection fraction. CONCLUSIONS Both clinical and genetic factors are associated with SVC arrhythmogenicity.

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.

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 (pp = 0.026). The results of this study indicate that zinc deficiency is a risk factor for CKD progression.

Background Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients’ prognosis. Methods Subjects with serum creatinine level for a baseline period over 1–3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Results Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m2. Among the subjects recruited, 15.81% had a low eGFR (

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 Results Although FMD tended to improve only in the dapagliflozin group, ΔFMD was comparable between the two groups. Analysis of patients with HbA1c >7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P Conclusions Dapagliflozin add-on therapy to metformin for 16 weeks improved endothelial function, as assessed by FMD, in patients with inadequately controlled early-stage T2DM. Improvement in oxidative stress may contribute to the improvement in FMD. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000018754)

Introduction This multi-center, prospective, controlled, open, and randomized three-arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function. Materials and Methods Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and

Tumor location in bladder neck has reported to be a prognostic factor for non-muscle-invasive bladder cancer (NMIBC). We investigated the impact of bladder neck involvement (BNI) on recurrence in NMIBC using time-dependent covariate analysis.We enrolled 585 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2000 to 2016 and were pathologically diagnosed with Ta and T1 NMIBC. Each patient at each recurrence was assigned to a separate time-dependent stratum with its own baseline hazard function according to the Prentice-Williams-Peterson gap time model for analyzing recurrent events.Over a median follow-up period of 41.3 months (interquartile range, 18.0-82.3 months), 253 (43.2%) patients experienced a total of 475 recurrences. Among the 1001 total transurethral resection procedures, BNI was observed in 122 (12.2%) cases. The 3-year cumulative recurrence rates of patients with and without BNI were 62.5% and 46.3%, respectively. Multivariable analysis revealed that number of tumors ≥ 4 (sub-hazard ratio [SHR], 1.48; P = .004), intravesical bacillus Calmette-Guérin therapy (SHR, 0.44; P .001), and BNI (SHR, 1.59; P = .004) were all independent predictors of recurrence. Assigning 1 point for each of these 3 predictive factors, the resulting scores enabled us to classify patients into 3 prognostic groups that were clearly stratified according to recurrence.Our time-dependent covariate analysis shows that BNI is a significant risk factor for recurrence in NMIBC. Our prognostic model incorporating BNI is an easy means of estimating recurrence risk and determining optimal management for individual patients.

Because hypotension during hemodialysis (HD) makes continuation of HD difficult and is associated with mortality, pressor approaches are necessary for patients with hypotension. However, the relationships between the pressor approaches and the risk of death have not been clarified yet. We analyzed data from a nationwide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (n = 29,309). The outcome was all-cause one-year death. The association between the use of pressor approaches and the outcome was examined using Cox proportional hazards models adjusted for baseline characteristics, propensity score matched analysis and Bayesian networks. The background features of the patients were as follows: male, 59.6%; average age, 64.5 ± 12.5 years; and patients with diabetes mellitus, 31.5%. The pressor group showed a higher risk of the outcome than the control group [adjusted hazard ratio (aHR) 1.33 (95% CI: 1.21, 1.47), p = 0.0001]. Propensity score matched analysis also showed that the matched-pressor group had a higher risk of the outcome than the matched-control group [aHR 1.30 (95% CI: 1.17, 1.45), p = 0.0001]. Moreover, the Bayesian network showed a direct causal relationship from the use of pressor approaches to the outcome. The use of oral vasopressors [aHR 1.20 (95% CI: 1.07, 1.35), p = 0.0018], intravenous injection of vasopressors [aHR 1.54 (95% CI: 1.32, 1.79), p = 0.0001] and normal saline [aHR 1.18 (95% CI: 1.05, 1.33), p = 0.0066] were associated with a high risk of the outcome. In conclusion, this study showed that the use of pressor approaches during HD may be an independent risk factor for death.

Identifying progressive early chronic kidney disease (CKD) patients at a health checkup is a good opportunity to improve their prognosis. However, it is difficult to identify them using common health tests. This worksite-based cohort study for 7 years in Japan (n = 7465) was conducted to evaluate the progression of CKD. The outcome was aggravation of the KDIGO prognostic category of CKD 7 years later. The subjects were male, 59.1%; age, 50.1 ± 6.3 years; and eGFR, 79 ± 14.4 mL/min/1.73 m2. The number of subjects showing CKD progression started to increase from 3 years later. Vector analysis showed that CKD stage G1 A1 was more progressive than CKD stage G2 A1. Bayesian networks showed that the time-series changes in the prognostic category of CKD were related to the outcome. Support vector machines including time-series data of the prognostic category of CKD from 3 years later detected the high possibility of the outcome not only in subjects at very high risks but also in those at low risks at baseline. In conclusion, after the evaluation of kidney function at a health checkup, it is necessary to follow up not only patients at high risks but also patients at low risks at baseline for 3 years and longer.

The relationship between protein–energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression. The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2–5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (

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.

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.

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

The palliative care team (PCT), nutrition support team (NST), and department of nutrition in our hospital developed a special soup service for patients with terminal cancer. We evaluated the usefulness of this soup service for improving the mood in patients with advanced digestive cancer with severe anorexia.We retrospectively reviewed the clinical data of 18 patients with advanced cancer originating in digestive organs who received soup service at our institution between 2015 and 2016. Members of the PCT, NST, and a licensed cook visited the bedside of each patient and served them a cup of soup twice a week.Fifteen patients (83%) were able to taste the soup with no adverse events, and 11 (73%) of them enjoyed the taste of the soup. In the five patients who died in our hospital during the service, the time between their last soup intake and death ranged from two to seven days (median three days).Even terminally ill patients suffering from advanced digestive cancer with severe anorexia were able to enjoy the taste of the soup served to them. The establishment of special meal service, such as this soup service, may not only relieve their stress but also support the strength of living and help improve their spiritual quality of life.

Determination of daily protein intake in the management of chronic kidney disease (CKD) requires precision. Inaccuracies in recording dietary intake occur, and estimation from total urea excretion presents hurdles owing to the difficulty of collecting whole urine for 24 h. Spot urine has been used for measuring daily sodium intake and urinary protein excretion. In this cross-sectional study, we investigated whether urea nitrogen (UN) concentration in spot urine can be used to predict daily protein intake instead of the 24-h urine collection in 193 Japanese CKD patients (Stages G1–G5). After patient randomization into 2 datasets for the development and validation of models, bootstrapping was used to develop protein intake estimation models. The parameters for the candidate multivariate regression models were male gender, age, body mass index (BMI), diabetes mellitus, dyslipidemia, proteinuria, estimated glomerular filtration rate, serum albumin level, spot urinary UN and creatinine level, and spot urinary UN/creatinine levels. The final model contained BMI and spot urinary UN level. The final model was selected because of the higher correlation between the predicted and measured protein intakes r = 0.558 (95 % confidence interval 0.400, 0.683), and the smaller distribution of the difference between the measured and predicted protein intakes than those of the other models. The results suggest that UN concentration in spot urine may be used to estimate daily protein intake and that a prediction formula would be useful for nutritional control in CKD patients.

Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients.Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential.Twenty-five of twenty-seven patients completed study. The mean serum uric acid levels in the topiroxostat-treated arm was significantly lower than it in the allopurinol-treated arm time-dependently (P 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat-arm (*P = 0.0035), but not in allopurinol-arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation-reduction potential, and capacity oxidation-reduction potential between pre and post treatment of both drugs.It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.

Patients with end-stage renal disease undergoing hemodialysis (HD) have an elevated risk of cardiovascular disease-related morbidity and mortality. To prevent from such a life-threatening event, the continuous blood pressure (BP) monitoring system may contribute to detect BP decline in early stages and may help to do appropriate disposal. Our research team has introduced an electronic stethoscope (Asahi Kasei Co, Ltd., Tokyo, Japan), which translates sound intensity of Arteriovenous Fistula (AVF) to BP data using the technique of Fourier transformation that can predict continuous BP non-invasively. This study, we investigated whether electronic stethoscope-guided estimated BP (e-BP) would actually reflect systolic BP measured by sphygmomanometer (s-BP), and whether e-BP could predict fall of BP during HD. Twenty-six patients who underwent HD treatment in our hospital were evaluated prospectively. We obtained sound intensity data from the electronic stethoscope which was equipped with the return line of HD. Then, the data were translated into e-BP data to be compared with s-BP. Correlation of total of 315 data sets obtained from each method was examined. An accuracy of diagnosis of intra-dialytic hypotension (IDH) was evaluated. Total of 315 data sets were obtained. A close correlation was observed between e-BP and s-BP (r = 0.887, p

When adenoids (Ad) and tonsils (Tn) become hypertrophied, craniofacial and general body growth is affected. However, there are no objective explicit criteria for evaluating the size of the Ad and Tn, and their respective growth patterns remain unclear. This study determined the average proportions of the Ad and Tn sizes to the upper airway area at various developmental stages in Japanese individuals. Lateral cephalometric radiographs were obtained from 300 Japanese children and teenagers (150 boys and 150 girls, aged 6–20 years), and the respective proportions of Ad to the nasopharynx (Ad/Np) and Tn to the oropharynx (Tn/Op) in the upper airway were determined. Average and standard deviation (SD) were calculated for each of the 5 age groups: lower primary school, upper primary school, junior high school, senior high school, and young adults. We investigated the correlation between age and growth patterns of Ad and Tn, and determined the average Ad/Np and Tn/Op. There was an age-related decrease in Ad and Tn size, and a significant positive correlation between Ad/Np and Tn/Op values in the upper primary school group. Both Ad/Np and Tn/Op decrease as individuals approach adulthood. However, the growth patterns of the Ad/Np and Tn/Op differ from each other.

Aim Proteinuria is known to be an independent risk factor of end‐stage renal disease (ESRD). But the associations between changes in dipstick proteinuria and the risk of ESRD in the general population and its appropriate observation period to predict incident ESRD are unknown. Methods We assessed the changes in dipstick proteinuria in 69 021 participants aged ≥20 years who participated in health check‐ups from 1993 and more than once until 1996 in Okinawa, Japan. Development of ESRD until 2011 was identified using dialysis registry. Cox proportional hazards model and receiver operating characteristic (ROC) curve were used. Results At baseline, proteinuria (±) and ≥(1+) were observed in 2.4% and 1.2% of total subjects. 1.5% of subjects had decreased and 9.4% of subjects had increased their proteinuria level after 2 years. After adjustment for confounding factors, hazard ratios (95% confidence interval) of ESRD for subjects with proteinuria change ≤ − 1, +1, +2, +3, and +4 level during 2 years compared to subjects with no change were 0.89 (0.43–1.87), 3.18 (2.21–4.60), 8.01 (5.55–11.55), 11.17 (6.59–19.95), and 16.59 (5.95–46.25), respectively. Heterogeneity existed between changes in proteinuria level during 1 or 3 years and the risk of ESRD among baseline proteinuria. Area under the ROC curve (95%CI) to predict ESRD by increase in proteinuria level during 1, 2, and 3 years were 0.650 (0.623–0.679), 0.779 (0.751–0.808), and 0.778 (0.748–0.808), respectively. Conclusions The changes in dipstick proteinuria were an independent predictor of ESRD in the general population. Changes in proteinuria over 2 years may be appropriate for the risk prediction of ESRD., Summary at a Glance Changes in dipstick proteinuria were an independent predictor of ESRD in the general population. This study on a large Japanese population of CKD with proteinuria shows that increase in dipstick proteinuria over 2 years may be appropriate for risk prediction of ESRD.

We evaluated the influence of catheter sampling position and size on left adrenal venous sampling (AVS) in patients with primary aldosteronism (PA) and analyzed their relationship to cortisol secretion. This retrospective study included 111 patients with a diagnosis of primary aldosteronism who underwent tetracosactide-stimulated AVS. Left AVS was obtained from two catheter positions - the central adrenal vein (CAV) and the common trunk. For common trunk sampling, 5-French catheters were used in 51 patients, and microcatheters were used in 60 patients. Autonomous cortisol secretion was evaluated with a low-dose dexamethasone suppression test in 87 patients. The adrenal/inferior vena cava cortisol concentration ratio [selectivity index (SI)] was significantly lower in samples from the left common trunk than those of the left CAV and right adrenal veins, but this difference was reduced when a microcatheter was used for common trunk sampling. Sample dilution in the common trunk of the left adrenal vein can be decreased by limiting sampling speed with the use of a microcatheter. Meanwhile, there was no significant difference in SI between the left CAV and right adrenal veins. Laterality, determined according to aldosterone/cortisol ratio (A/C ratio) based criteria, showed good reproducibility regardless of sampling position, unlike the absolute aldosterone value based criteria. However, in 11 cases with autonomous cortisol co-secretion, the cortisol hypersecreting side tended to be underestimated when using A/C ratio based criteria. Left CAV sampling enables symmetrical sampling, and may be essential when using absolute aldosterone value based criteria in cases where symmetrical cortisol secretion is uncertain.

Background/Aims: Non-volatile acid is produced by metabolism of organic sulfur in dietary protein, and promotes kidney damage. We investigated the role of dietary acid load, in terms of net endogenous acid production (NEAP), in chronic kidney disease (CKD) progression. Methods: 217 CKD patients on low-protein diet with a normal serum bicarbonate level were enrolled in this retrospective cohort study in Japan. The primary outcome was 25% decline in estimated glomerular filtration rate (eGFR) or start of dialysis. Their NEAP was measured every 3 months. The patients were categorized into four groups on the basis of quartiles of NEAP every 3 months. The groups were treated as time-dependent variables. Results: The average age (SD) was 70.6 (7.1) years; eGFR 23.5 (14.2) ml/min/1.73 m2. Analysis using extended Cox models for the NEAP groups adjusted for baseline characteristics (referring to group 1 showing the lowest NEAP) showed that high NEAP was associated with a high risk of CKD progression; group 2, adjusted hazard ratio (HR) 3.930 (95% confidence interval (CI) 1.914, 8.072); group 3, adjusted HR 4.740 (95% CI 2.196, 10.288); group 4, adjusted HR 4.303 (95% CI 2.103, 8.805). Logistic regression analysis adjusted for baseline characteristics showed that the occurrence of hypoalbuminemia or hyperkalemia was associated with low serum bicarbonate level and the presence of complications at baseline, but not with NEAP. Conclusion: In elderly CKD patients, our findings suggest that high NEAP is independently associated with CKD progression. The decrease in NEAP may be an effective kidney-protective therapy.

Background Current status and clinical significance of interventional nephrology has not been reported from Japan. Methods Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists’ involvement to each procedure and annual procedure volume were examined. Results 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran–Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p

Elevated white blood cell (WBC) count is a well-known predictor of chronic kidney disease (CKD) progression. However, elderly patients commonly fail to develop a high WBC count in response to several diseased states and may instead present a low WBC count. Therefore, we hypothesized that low WBC count, in addition to high WBC count, is associated with CKD progression in the elderly. We conducted a prospective cohort study using 3-year follow-up data from the CKD Research of Outcomes in Treatment and Epidemiology study. In the present study, participants aged over 60 years with pre-dialysis CKD stages G2–G5 were eligible. Patients were stratified into three groups according to WBC count using tertiles (T). The primary outcome was a composite of end-stage renal disease and a 50% reduction in estimated glomerular filtration rate. Data were analyzed using Cox proportional hazard models with adjustments for covariates. We enrolled 697 patients (males, 69%). The median WBC count was 6100 cells/µl (T1

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.

Anti-centromere antibody (ACA), a typical autoantibody of systemic sclerosis, is also detected in primary biliary cirrhosis (PBC). However, its pathogenic role is not fully understood. The aim of this study was to determine the association between ACA and kidney function in PBC.A cohort of 37 patients diagnosed as having PBC from July 2001 to November 2011 at Yokosuka Kyosai Hospital was retrospectively analyzed for a follow-up period of 12 months. The annual rate of estimated glomerular filtration rate (eGFR) decline within 1 year after the diagnosis was evaluated. The factors associated with eGFR decline were evaluated by linear regression analysis and logistic regression analysis.Overall, 37 PBC patients were included, of whom 12 (32%) had ACA. The patients with ACA had a lower eGFR (65.9 ± 19.9 vs. 80.3 ± 12.1 mL/min/1.73 m(2), P = 0.01), a higher likelihood of chronic kidney disease (CKD) (58 vs. 4%, P = 0.0005), and a higher rate of annual eGFR decline (-4.3 ± 5.1 vs. 0.2 ± 4.6 mL/min/year, P = 0.01) than those without ACA. Univariate regression analysis and multivariate regression analysis adjusted for potential cofounders including age, eGFR, sex, diabetes mellitus, and hypertension showed that ACA was associated with eGFR decline (P = 0.011 and 0.017, respectively). Multivariate logistic regression analysis adjusted for these cofounders showed that ACA was associated with eGFR decline less than -4 mL/min/year (odds ratio 7.21, 95% confidence interval 0.93-56.1, P = 0.059).ACA is an independent risk factor for CKD in PBC. Evaluation of ACA and kidney function is necessary to prevent CKD progression in PBC patients.

Medical Evidence Report Form CMS-2728 data is frequently used to study US dialysis patients, but the validity of these data have been called into question. We compared predialysis erythropoietin use as recorded on Form CMS-2728 with claims data as part of an assessment of quality of care among hemodialysis patients. Medicare claims were linked to Form CMS-2728 data for 18,870 patients. Dialysis patients, 67 years old or older, who started dialysis from 1 June 2005 to 31 May 2007 were eligible. Logistic and multivariate regressions were used to compare the use of either Form CMS-2728 or the corresponding claims data to predict mortality and the probability of meeting target hemoglobin levels. The sensitivity, specificity, and kappa coefficient for the predialysis erythropoietin indicator were 58.0%, 78.4%, and 0.36, respectively. Patients with a predialysis erythropoietin claim were less likely to die compared with patients without a claim (odds ratio = 0.80 and 95% confidence interval = 0.74-0.87), but there was no relationship observed between predialysis care and death using only Form CMS-2728 predictors. At the facility level, a predialysis erythropoietin claim was associated with a 0.085 increase in the rate of meeting target hemoglobin levels compared with patients without a claim (p = 0.041), but no statistically significant relationship was observed when using the Form CMS-2728 indicators. The agreement between Form CMS-2728 and claims data is poor and discordant results are observed when comparing the use of these data sources to predict health outcomes. Facilities with higher agreement between the two data sources may provide greater quality of care.