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Sphingomyelin phosphodiesterase 3 ( Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue. [ABSTRACT FROM AUTHOR]

Iwayama T, Yanagita M, Mori K, Sawada K, Ozasa M, Kubota M, Miki K, Kojima Y, Takedachi M, Kitamura M, Shimabukuro Y, Hashikawa T, Murakami S. Adiponectin regulates functions of gingival fibroblasts and periodontal ligament cells. J Periodont Res 2012; 47: 563-571. © 2012 John Wiley & Sons A/S Background and Objective: Adiponectin is a cytokine constitutively produced by adipocytes and exhibits multiple biological functions by targeting various cell types. However, the effects of adiponectin on primary gingival fibroblasts and periodontal ligament cells are still unexplored. Therefore, we investigated the effects of adiponectin on gingival fibroblasts and periodontal ligament cells. Material and Methods: The expression of adiponectin receptors (AdipoR1 and AdipoR2) on human gingival fibroblasts (HGFs), mouse gingival fibroblasts (MGFs) and human periodontal ligament (HPDL) cells was examined using RT-PCR and western blotting. HGFs and MGFs were stimulated with interleukin (IL)-1β in the presence or absence of adiponectin, and the expression of IL-6 and IL-8 at both mRNA and protein levels was measured by real-time PCR and ELISA, respectively. Furthermore, small interfering RNAs (siRNAs) in MGFs were used to knock down the expression of mouse AdipoR1 and AdipoR2. The effects of adiponectin on the expression of alkaline phosphatase ( ALP) and runt-related transcription factor 2 ( Runx2) genes were evaluated by real-time PCR. Mineralized nodule formation of adiponectin-treated HPDL cells was revealed by Alizarin Red staining. Results: AdipoR1 and AdipoR2 were expressed constitutively in HGFs, MGFs and HPDL cells. Adiponectin decreased the expression of IL-6 and IL-8 in IL-1β-stimulated HGFs and MGFs. AdipoR1 siRNA in MGFs revealed that the effect of adiponectin on reduction of IL-6 expression was potentially mediated via AdipoR1. Adiponectin-treated HPDL cells promoted the expression of ALP and Runx2 mRNAs and up-regulated ALP activity. Furthermore, adiponectin enhanced mineralized nodule formation of HPDL cells. Conclusion: Our observations demonstrate that adiponectin exerts anti-inflammatory effects on HGFs and MGFs, and promotes the activities of osteoblastogenesis of HPDL cells. We conclude that adiponectin has potent beneficial functions to maintain the homeostasis of periodontal health, improve periodontal lesions, and contribute to wound healing and tissue regeneration. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) 16, 812-817 Objectives: Tobacco smoking has been suggested to be one of the important risk factors of developing periodontal disease. Although epidemiological studies have shown the detrimental effects of smoking on periodontal disease, the effects of smoke compounds on gingival tissue are not well understood. The aim of this study was to evaluate the effects of nicotine, which is the major component of the thousands of chemicals that constitute cigarette smoke, for cytodifferentiation of murine periodontal ligament (MPDL) cell. Materials and methods: Expression of nAChR subunits on MPDL cells was examined using RT-PCR. The effects of nicotine on gene expression of extracellular matrices and osteoblastic transcription factors were evaluated by quantitative RT-PCR. Mineralized nodule formation of nicotine-treated MPDL cells was characterized by alizarin red staining. Results: Murine periodontal ligament cells expressed several subunits of nAChR, which have functional calcium signals in response to nicotine. Gene expression of extracellular matrices and osteoblastic transcription factors were reduced in nicotine-treated MPDL cells. In addition, mineralized nodule formation was inhibited in MPDL cells in the presence of nicotine. Conclusion: Our findings indicate that nicotine may negatively regulate the cytodifferentiation and mineralization of MPDL cells. [ABSTRACT FROM AUTHOR]

Background: Patients with low-to-normal body mass index (BMI; < 25.0 kg/m 2 ) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials., Methods: This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m 2 ). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category., Results: Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m 2 , 1.9% [n = 5,350]; 20.0-22.4 kg/m 2 , 8.5% [n = 23,818]; and 22.5-24.9 kg/m 2 , 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m 2 , HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m 2 , HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m 2 , HR [95%CI] = 0.92 [0.84 to 1.01])., Conclusions: The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors., (© 2024. The Author(s).)

Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear., Materials and Methods: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease)., Results: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001)., Conclusions: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes., (© 2024 John Wiley & Sons Ltd.)

Purpose: Imaradenant is a novel potent and selective adenosine A2A receptor antagonist that is hypothesized to reduce immune suppression in the tumor microenvironment. This phase I, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and anti-tumor activity of imaradenant., Methods: Japanese patients with advanced solid malignancies received imaradenant 50 mg (n = 3) or 75 mg (n = 7) once daily (QD). The primary objective was safety and tolerability, and the secondary objectives were pharmacokinetics and anti-tumor activity., Results: The median treatment duration was 2.10 months and 2.14 months for the 50- and 75-mg QD cohorts, respectively. The most common adverse events were nausea, malaise, decreased appetite, and vomiting. Five patients (50%) reported adverse events that were considered causally related to imaradenant; three patients had Grade 2 adverse events of malaise, nausea, and diarrhea. No deaths or serious adverse events occurred. The median times of maximum observed concentrations sampled after a single dose in the 50- and 75-mg QD cohorts were 1.08 h (range, 0.95-1.95) and 2.00 h (range, 0.92-5.52), respectively. There was little accumulation after multiple dosing, with geometric mean accumulation ratios of maximum concentration of 1.3 (50-mg QD) to 1.4 (75-mg QD) and area under the concentration-time curve 0-24 of 1.4 (50-mg QD) to 1.5 (75-mg QD). The best objective response was stable disease (3/10)., Conclusion: No new or unexpected safety concerns were identified, and imaradenant had an acceptable safety profile at both 50- and 75-mg QD., Clinicaltrials: gov identifier NCT03980821 (June 10, 2019)., (© 2023. The Author(s).)

Background: The revised KDIGO guidelines recommend maintaining systolic blood pressure (sBP) < 120 mmHg in patients with chronic kidney disease (CKD), based on cardiovascular and survival benefits. However, the renal benefit of this strategy remains less clear., Methods: We used data of routine health checkups in Japan. Persons whose estimated glomerular filtration rate (eGFR) was < 60 mL/min/1.73 m 2 in 2015 without end-stage disease were followed until 2020. We estimated the 5-year benefit of hypothetical targeted sBP control using parametric g-formula modeling, accounting for both time-fixed and time-varying confounding variables. Four sensitivity analyses, including analysis using a marginal structural model (MSM) and positive control outcome analysis, were also done., Results: We enrolled 28,972 persons with CKD (median age: 54 years, male: 69%, baseline eGFR [median]: 56 mL/min/1.73m 2 ). As compared with the natural course without a targeted intervention, there was no renoprotective effect of targeted sBP control, with a 5-year difference in eGFR of 0.65 mL/min/1.73 m 2 (95% confidence interval - 0.42 to 1.65 mL/min/1.73 m 2 ). MSM analysis found a similar result. In contrast, the positive control analysis using the cardiovascular outcome showed that targeted sBP control would reduce the cardiovascular disease incidence by 6.0% over 5 years., Conclusions: A targeted sBP control strategy maintaining < 120 mmHg may not yield a renoprotective effect for patients with stage 3-4 CKD, although it was expected to offer a cardiovascular benefit. Future research may be warranted in higher-risk populations, such as elderly people or those with more advanced kidney disease., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Competing Interests: M. Yanagita reports receiving research funding from Boehringer Ingelheim and Tanabe Mitsubishi; reports receiving honoraria from Astellas, Chugai, Kyowa Kirin, and others for lectures; and reports having other interests/relationships with the Japanese Society of Nephrology; International Society of Nephrology. The remaining author has nothing to disclose.

Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (V d ) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and V d of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

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 m 2 , 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 m 2 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 ( P heterogeneity ≥ 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., (© 2021 by the American Diabetes Association.)

Background: It has been pointed out that prolonged television (TV) viewing is one of the sedentary behaviors that is harmful to health; however, the association between socioeconomic status (SES) and prolonged TV viewing time has not been sufficiently investigated in Japan., Methods: The study population are the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2752 adults. SES was classified according to the employment status, educational attainment, living status, and equivalent household expenditure (EHE). Prolonged TV viewing time was defined as more than or equal to 4 h of TV viewing per day. Multivariable logistic regression analyses were conducted to examine the association of SES with prolonged TV viewing time., Results: The mean TV viewing time was 2.92 h in all participants. Of 2752 participants, 809 (29.4%) prolonged TV viewing, and the mean TV viewing time of them was 5.61 h. The mean TV viewing time in participants without prolonged TV viewing time was 1.81 h. The mean TV viewing time was prolonged as age classes increased and significantly longer in aged ≥60 years. Prolonged TV viewing time was associated with not working for all age classes and sexes. Only among women, education attainment and living status were also associated with prolonged TV viewing time. For education attainment, the lower the received years of education, the higher odds ratios (OR) of prolonged TV viewing time. For living status, in women aged <60 years, living with others had a significantly higher OR compared to living with spouse. On the other hand, in women aged ≥60 years, living alone had a significantly higher OR. EHE did not have any significant associations with prolonged TV viewing time., Conclusions: In a general Japanese population, it should be noted that the association between SES and prolonged TV viewing time differed by age and sex. Particularly, it must draw attention to the prolonged TV viewing in elderly. The intervention in order to shorten TV viewing time needs to consider these attributes.

Hypertension is a heterogeneous disease for which role sharing in treatment between specialized facilities and small clinics is needed for efficient healthcare provision. However, the Japanese healthcare system has a "free access" attribute; therefore, nobody can control treatment resource allocation. We aimed to describe the current situation of role sharing by comparing antihypertensive therapies among different types of medical facilities. We analyzed 1% sampled Japanese medical insurance claims data related to outpatient care as of October 2014. We divided the target patients into four groups according to the size of the facilities that issued the insurance claim for them. Among these groups, we compared the number of antihypertensive drugs and proportion of difficult-to-treat hypertensive cases and performed a stratified analysis. The proportion of patients with hypertension and diabetes mellitus receiving renin-angiotensin-aldosterone system inhibitors (RAASis) as the first-choice drug was also compared. We identified 3465, 1797, 2323, and 34,734 claims issued from large, medium-sized, small hospitals, and clinics, respectively. The mean number of hypertensive drugs was 1.96, 1.87, 1.81, and 1.69, respectively, and the proportion of difficult-to-treat hypertensive cases was 18.9, 17.0, 14.3, and 12.0%, respectively, with both showing significant differences. Stratified analysis showed similar results. The proportion of patients with hypertension and diabetes mellitus receiving RAASis as the first-choice drug was higher in large hospitals than in clinics. In conclusion, facility size is positively associated with the number of antihypertensive drugs and proportions of difficult-to-treat hypertensive cases. This finding describes the current role sharing situation of hypertension therapy in the Japanese healthcare system with a "free-access" attribute.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Background: The 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., Methods: In 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., Results: Logistic 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., Conclusions: We determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study., Competing Interests: The authors have no conflicts of interest to declare.

Background: The prognosis of pneumonia in patients with advanced stage chronic kidney disease (CKD) remains unimproved for years. We attempt to develop a simple and more useful scoring system for predicting in-hospital mortality for advanced CKD patients with pneumonia., Methods: Using the Diagnosis Procedure Combination database, we identified the in-hospital adult patients both with a record of pneumonia and stage 5 or 5D CKD as a comorbidity on admission between April 1, 2012 and March 31, 2016. Predictive variable selection was analyzed by multivariable logistic regression analysis, stepwise method, LASSO method and random forest method, and then develop a new simple scoring system seeking for highest c-statistics combination of variables in one sample data set for model development. Finally, we compared c-statistics of univariate logistic regression about new scoring system with c-statistics about "A-DROP" in the other sample data set., Result: We identified 8402 patients in 707 hospitals, and the total in-hospital mortality was 11.0% (437 patients) in development data set. Seven variables were selected, which includes age (male ≥ 70 years, female ≥ 75 years), respiratory failure, orientation disturbance, low blood pressure, the need of assistance in feeding or bowel control, severe or moderate thinness and CRP 200 mg/L or extent of consolidation on chest X-ray ≥ 2/3 of one lung. The c-statistics of univariate logistic regression was 0.8017 using seven variables, while that was 0.7372 using "A-DROP" CONCLUSION: In advanced CKD patients, if we select appropriate variables for predicting in-hospital mortality, simple scoring system may have better discrimination than "A-DROP".

Background: The 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., Methods: In 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., Results: The 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., Conclusions: We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study., Competing Interests: The authors have declared that no competing interests exist.

Background: The quality of care received by a growing number of older patients with chronic kidney disease (CKD) has not been adequately examined., Objective: The objective of this study was to assess the quality of CKD care among older patients and to clarify its association with the incidence of end-stage renal disease (ESRD)., Research Design: This was a population-based cohort study., Subjects: Older (65 y and above) CKD patients diagnosed between October 2010 and September 2014 from the National Database of Health Insurance Claims of Japan., Measures: A composite quality score (QS) of 3 quality measures for CKD care during the 6 months after CKD diagnosis was computed. The validated quality measures included urine testing for proteinuria, nutritional guidance, and nonsteroidal anti-inflammatory drugs avoidance. To assess the association between the QS and ESRD incidence, we used instrumental variable analysis after stratification for the history of diabetes., Results: Among the 890,773 older CKD patients, 2.9% progressed to ESRD (incidence rate of 12.5 per thousand person-years). In total, 59.9% underwent urine testing, 4.5% received nutritional guidance, and 91.2% avoided regular use of nonsteroidal anti-inflammatory drugs. An instrumental variable analysis revealed that a higher QS was associated with-lower ESRD incidence in patients diagnosed with diabetes (hazard ratio: 0.25, 95% confidence interval: 0.24-0.27 for each point higher score) but not in patients without a diagnosis of diabetes (hazard ratio: 0.99, 95% confidence interval: 0.92-1.05)., Conclusion: Among older CKD patients, quality of CKD care varied between patients, and better quality of CKD care was associated with a lower ESRD incidence in patients with diabetes but not in nondiabetic patients.

Background: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women., Methods: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis., Results: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men., Conclusions: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

Background: Chronic kidney disease (CKD) is a public health challenge; however, evidence-based, optimal follow-up intervals for patients with CKD have not been identified. This study aimed to identify appropriate follow-up intervals for different stages of CKD., Methods: We studied 2682 patients with CKD. The number of patients experiencing a 50% increase in creatinine and those reaching end-stage renal failure were examined on the basis of their CKD stage. The renal function testing interval was defined as the estimated time for 0.1% of the patients with CKD to have a composite renal outcome, after adjusting for clinical risk factors. Transitions from CKD stage-based subgroups were analyzed using parametric cumulative incidence models. Other sensitivity analyses involved estimation of the time to renal event occurrence for 1% of patients., Results: Of the 913 patients (34%) who had a composite renal event, 29 had stage 3A (10.5%), 151 had stage 3B (16.3%), 429 had stage 4 (41.0%), and 304 had stage 5 CKD (70.9%). The estimated renal function testing intervals for patients with CKD were 6.0 months for stage 3A, 3.4 months for stage 3B, 2.0 months for stage 4, and 1.2 months for stage 5., Conclusions: The optimal follow-up intervals were longer for patients with lower CKD stages. These estimates are longer than those recommended by the current guidelines and serve as a reference for nephrologists in selecting an appropriate follow-up interval for each patient., Trial Registration: UMIN clinical trial registry number: UMIN000020038.

As Japan becomes a super-aging society, presentation of the best ways to provide medical care for the elderly, and the direction of that care, are important national issues. Elderly people have multi-morbidity with numerous medical conditions and use many medical resources for complex treatment patterns. This increases the likelihood of inappropriate medical practices and an evidence-practice gap. The present study aimed to: derive findings that are applicable to policy from an elucidation of the actual state of medical care for the elderly; establish a foundation for the utilization of National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), and present measures for the utilization of existing databases in parallel with NDB validation.Cross-sectional and retrospective cohort studies were conducted using the NDB built by the Ministry of Health, Labor and Welfare of Japan, private health insurance claims databases, and the Kyoto University Hospital database (including related hospitals). Medical practices (drug prescription, interventional procedures, testing) related to four issues-potential inappropriate medication, cancer therapy, chronic kidney disease treatment, and end-of-life care-will be described. The relationships between these issues and clinical outcomes (death, initiation of dialysis and other adverse events) will be evaluated, if possible.

Background: In order to keep up the optimal iron status in chronic hemodialysis patients, it is important to know how much iron is lost due to hemodialysis. Residual blood associated with the hemodialysis procedure together with blood sampling inevitably causes the loss of iron in chronic hemodialysis patients. Recent advances in hemodialysis techniques might have reduced this complication. In this cross-sectional study, we directly measured total iron loss by hemodialysis., Methods: Two hundred thirty-nine patients who received chronic hemodialysis at Otowa Memorial Hospital were enrolled; 65.7% of patients were men, and mean age was 67 ± 6.4 years (mean ± SD) and 43.2% were diabetic. Residual blood in blood tubing set and dialyzer after rinse back with saline was collected and homogenized. The iron content including free, protein-bound and heme iron was measured using an atomic absorption spectrometry., Results: The mean iron content in residual blood was 1,247.3 ± 796.2 µg (mean ± SD) and the median was 1,002 µg (95% CI 377.6-3,461.6 µg), indicating 160.8 mg (95% CI 58.9-540.0 mg) iron loss annually when hemodialysis was performed 156 times a year. Fifty milliliter whole blood for monthly blood test and another 2 ml of whole blood lost by paracentesis at every dialysis session contains 228.6 and 118.9 mg iron at 11 g/dl hemoglobin, respectively. Therefore, an annual total iron loss due to hemodialysis comes to 508.3 mg (95% CI 406.4-887.5 mg)., Conclusions: Five hundred milligram of annual iron supplementation might be sufficient to maintain iron status in hemodialysis patients, which is less than the dose recommended as 1,000-2,000 mg a year. Further study will be required to verify this iron supplementation dosage with recent hemodialysis procedure., (© 2016 S. Karger AG, Basel.)

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid clearance and is associated with acute renal failure (ARF). An 18-year-old sumo wrestler developed ARF after anaerobic exercise. Several hours after the exercise, he had a pain in the loins with oliguria, headache, and nausea. On admission, his serum uric acid was decreased despite the elevation of serum creatinine (9.5 mg/dL). The level of creatine kinase was normal and there was no myoglobinuria or urolithiasis. Magnetic resonance imaging showed no significant abnormality. Renal function improved completely within 2 weeks of hydration treatment. After remission, hypouricemia became obvious (1.0 mg/dL) from the initial level of uric acid (6.1 mg/dL) and fractional excretion of uric acid was 49%. Polymerase chain reaction of a urate anion exchanger known to regulate blood urate level (SLC22A12 gene: URAT1) demonstrated that homozygous mutations in exon 4 (W258X). Both parents showed heterozygous mutation of the URAT1 gene, but both siblings showed no mutation. Thus, we describe a Japanese sumo wrestler of familial renal hypouricemia complicated with anaerobic exercise-induced ARF, with definite demonstration of genetic abnormality in the responsible gene, URAT1.

Objective: The objective of this study was to examine the relation of physical performance measures with depressive symptoms in older men., Method: A cross-sectional, multivariate comparison of several measures of upper- and lower-extremity performance and their relation with depressive symptoms was performed in 2,856 older Japanese American men, aged 71-93 years, who participated in the fourth examination of the Honolulu Heart Program. Depressive symptoms were measured using an 11-item version of Center for Epidemiologic Studies Depression (CES-D) Scale. A score of at least 9 (from a maximum score of 33) is considered clinically significant. Timed functional performance tests, including walking and repeated chair stands, were used to assess lower-extremity performance; handgrip strength was used as an indicator of upper-extremity performance., Results: Two hundred eighty-three participants (9.9%) had a score of 9 or greater on the 11-question CES-D Scale and were considered to be at high risk for depression. Time to walk 10 feet and time to complete five chair stands were significantly longer in those with depressive symptoms, whereas handgrip strength was significantly lower. Only the association of gait speed (time to walk 10 feet) and depressive symptoms remained significant when all physical performance measures were simultaneously included in a multivariate analysis., Conclusion: These results demonstrate physical performance measures, particularly gait speed, may be important potential correlates of depression in community-dwelling older men.