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Background Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis. Methods DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries. Results The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews). Conclusions The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting.

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

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

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.

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.

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.

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

Background: Early chronic kidney disease (CKD) diagnosis in patients with type 2 diabetes (T2D) followed by guideline-recommended interventions are key to slowing CKD progression, but adherence to screening recommendations is suboptimal. Inside CKD models the global clinical and economic burden of CKD using country-specific, patient-level microsimulation models. We model the effects of targeted implementation of urine albumin:creatinine ratio (UACR) measurement and intervention in patients with T2D. Methods: We used the Inside CKD microsimulation to model the impact of measuring UACR during routine primary care visits with subsequent intervention in patients with T2D aged ≥45 years, versus current practice. Virtual populations were constructed using published country-specific data on demographics, CKD, T2D, comorbidities and complications. Results: Preliminary data for three countries show that in 2020-2025, measurement of UACR in patients with T2D would prevent CKD progression to stages 3b-5 in 80 000 patients in the UK, 350 000 in the US and 70 000 in Canada (Figure). Associated cost savings would be £90M, $5B and C$1.7B. More countries will be analysed. Conclusion: Preliminary data show that routine UACR measurement with subsequent intervention could potentially reduce the global burden of CKD and healthcare costs in patients with T2D, and improve outcomes. Disclosure S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen. S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca

Background: Inside CKD aims to model the future global clinical and economic burden of chronic kidney disease (CKD). Type 2 diabetes (T2D) is a leading cause of CKD, and concomitant CKD and T2D place a significant burden on healthcare systems worldwide. Methods: We used the Inside CKD country-specific, patient-level microsimulation to model global healthcare costs for patients with concomitant CKD and T2D from 2020 to 2025. We constructed virtual populations using country-specific data including demographics, prevalence of CKD (by stage), T2D and complications, and direct costs, from multiple published sources (e.g., NHANES for US; HSE for UK). Results: Preliminary results from three countries show that annual healthcare costs for patients with both CKD and T2D are expected to increase from 2020 to 2025 (US, $51.1B-95.3B; Canada, C$6.5B-11.5B; UK, £2.3B-2.7B) (Figure). Costs attributable to CKD stage 4 are expected to increase the most (US, 4-9% of overall costs; Canada, 9-13%; UK, 7-11%). Conclusion: Healthcare costs for patients with both CKD and T2D are projected to increase in the UK, US and Canada from 2020 to 2025. Later CKD stages are associated with more pronounced cost increases, likely due to both increased prevalence and greater treatment complexity. Early diagnosis and interventions to slow CKD progression are needed to reduce the economic burden of concomitant stage 3-5 CKD and T2D. Disclosure J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen . S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca

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.

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

Background and Aims Chronic kidney disease (CKD) is a debilitating and costly condition, with an estimated global prevalence of approximately 10%. Progression of CKD is associated with end-stage renal disease, cardiovascular events and premature mortality, as well as increased requirement for renal replacement therapies (RRTs), which are associated with significant healthcare costs and resource use. Furthermore, patients with CKD often have additional comorbidities, which are associated with CKD progression and increased costs. The trajectories of CKD prevalence, progression, outcomes and the related costs are therefore critical considerations for public health and policy planning. Using country-specific, patient-level microsimulation, Inside CKD aims to model the global clinical and economic burden of CKD from 2020 to 2025. Method We used the Inside CKD microsimulation to model the economic burden of CKD in the Americas and Asia-Pacific region. We developed a virtual general population for each country using national survey data and relevant data from published literature. Data inputs included country demographics, the prevalence of CKD and RRT, comorbidities and complication rates as well as associated healthcare costs. CKD stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 recommendations and patients were categorized according to estimated glomerular filtration rate and albuminuria status. We calibrated the RRT modelling against historical trends from country-specific renal registries. We conducted model validation and calibration using established methods for health economic modelling. Here, we report the results from the US and Canada analyses, with further analyses currently underway for additional countries in the Americas and Asia-Pacific region. Results Initial results for the US and Canada revealed that, between 2020 and 2025, annual healthcare costs associated with CKD will increase linearly from US$232.3B to US$376.2B in the US and from C$21.4B to C$34.1B in Canada (this figure does not include complication costs). In the US, the largest absolute increase in cost was observed in CKD stage 3a ($98.4B); however, CKD stage 4 had the largest relative increase in cost with an approximately three-fold increase (US$7.30B to US$23.3B). In Canada, the largest absolute increase in cost was observed in CKD stage 3a (C$5.84B); whereas CKD stage 5 had the largest relative increase in cost with an approximately five-fold increase (C$0.27B to C$1.41B). By 2025, costs associated with CKD will increase across all age categories (18–34, 35–64 and 65+ years) in both countries. In the US, the 35–64 age group had the largest absolute increase in costs with an increase of $74B (US$58.3B to US$132B). The largest relative increase in cost was observed in the 18–34 age category, with approximately a three-fold increase in costs (US$3.76B to US$10.2B). In Canada, the 65+ age group had the largest absolute increase in costs with an increase of C$7.9B (C$16.4B to C$24.3B). Both the 18–34 and 35–64 age categories had the largest relative increase in costs, with an approximately two-fold increase (C$0.25B to C$0.49B and C$4.77B to C$9.31B, respectively). Conclusion Initial results from Inside CKD demonstrate that CKD poses a significant economic burden over the next 5 years. CKD stage 3a was associated with the most pronounced cost increases in both the US and Canada, likely due to the increased prevalence of this stage. In the US, the largest increase in CKD costs was observed in the 35–64-year-old ‘working’ population, whereas the largest increase in Canada was observed in the 65 years old and over population. Further policy interventions aimed at early diagnosis and proactive management should be considered to slow disease progression, improve patient outcomes and reduce the economic burden associated with CKD.

Background and Aims With an estimated global prevalence of 10%, chronic kidney disease (CKD) and its associated complications place a substantial strain on healthcare systems worldwide, which is compounded by the burden of undiagnosed CKD. Early CKD diagnosis followed by guideline-recommended interventions can improve patient outcomes and reduce associated healthcare-related costs, particularly by delaying or preventing the development of complications and progression to kidney failure. Urinary albumin-to-creatinine ratio (UACR) can be used to screen for CKD, but adherence to screening recommendations is suboptimal in routine care. Inside CKD aims to model the global clinical and economic burden of CKD using country-specific, patient-level microsimulation models. We used the Inside CKD microsimulation to model the potential clinical and economic impacts of routine measurement of UACR followed by appropriate intervention in patients aged 45 years and over in the US and Canada. Method The Inside CKD microsimulation model was used to model the clinical and economic impacts associated with measurement of UACR with subsequent appropriate intervention during routine primary care visits versus current practice in individuals aged 45 years and over. The model covers the period 2020–2025. In preliminary analyses, virtual populations representing the general populations of the US and Canada were constructed using published country-specific data, including demographics, prevalence of CKD and comorbidities (type 2 diabetes, uncontrolled hypertension and heart failure), incidence of complications (heart failure, myocardial infarction, stroke and acute kidney injury) and costs associated with CKD. The model also included parameters relating to the proportion of patients who visit a primary care physician at least once a year, the proportion of patients who agreed to UACR measurements, and the diagnostic sensitivity and specificity of UACR measurements. The modelling is being expanded to additional countries in the Americas and the Asia-Pacific region. Results Preliminary results from the US and Canada show that over the 2020–2025 period routine measurement of UACR during primary care visits followed by appropriate intervention could prevent progression to CKD stages 3b–5 in approximately 1.3M patients in the US and 160 000 in Canada, compared with current clinical practice, with linear increases in the cumulative numbers of prevented cases (Figure). Associated savings in healthcare costs in 2025 are projected to be approximately US$16B in the US and C$2.5B in Canada, corresponding to a reduction in cost for that year of 4.4% and 7.4%, respectively, compared with current clinical practice. Conclusion Preliminary results from the Inside CKD microsimulation model in the US and Canada show that routine measurement of UACR with subsequent intervention in primary care would prevent progression to CKD stages 3b–5 in a substantial number of patients compared with current screening practices, and could therefore decrease associated healthcare costs considerably. This analysis is being extended to further countries in the Americas and the Asia-Pacific region.

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 [

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

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.

Background and Aims The malnutrition-inflammation-complex (MIC) is a risk factor for mortality and lower quality of life in haemodialysis (HD) patients. The identification of MIC and its risk factors, which include the limited ability to perform functional status (FS), is key to improve the patient experience on HD. Our study investigates the association of MIC and FS combinations with mortality in HD patients. Method We analysed data from a cohort of 5465 HD patients from Australia, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, and United Kingdom, enrolled in the Dialysis Outcomes and Practice Patterns Study phases 4 (2009-2011) and 5 (2012-2015). MIC syndrome was defined as low serum albumin (3mg/L in Japan; >10 mg/L elsewhere). Poor functional status was defined as the sum of scores from the self-reported limitations in the Katz Index of Independence in Activities of Daily Living (score ranges from 0 to 5) and the Lawton-Brody Instrumental Activities of Daily Living Scale (score ranges from 0 to 8) less than 11. We investigated the association between combinations of MIC (+/-) and FS (low/high) with death, using Cox proportional hazards models adjusted for possible confounders including patient demographics, comorbidity history, catheter use, serum creatinine, phosphorus levels, WBC count, haemoglobin level, and time on dialysis therapy. Results The prevalence of different combinations were: MIC-/High FS 57%, MIC-/Low FS 24%, MIC+/High FS 9%, and MIC+/Low FS 10%. Patients with MIC-/high FS were younger, better nourished, and had lower prevalence of comorbidities. Compared to this reference group, the adjusted hazard ratios [HR (95% CI)] for all-cause mortality were 1.56 (1.24-1.98) for MIC-/ low FS, 1.75 (1.32-2.32) for MIC+/ high FS, and 2.97 (2.31-3.82) for MIC+/ low FS groups. The adjusted HRs for infection-related mortality were 1.57 (0.91, 2.71) for MIC-/low FS, 1.67 (0.84, 3.31) for MIC+/High FS, and 5.45 (3.15, 9.45) for MIC+/low FS groups. Conclusion The combination of MIC and low FS is a strong predictor of mortality, and infectious mortality in particular, in HD patients. Identification of patients with MIC and FS status may plausibly help to direct interventions to improve patients’ experiences and lessen adverse clinical outcomes in the HD setting.

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.

Chronic kidney disease (CKD) patients are increasing in number globally because kidney function is affected by aging and lifestyle habits. Malnutrition, muscle weakness, and a decline in activities of daily living (ADL) are often observed in elderly CKD patients and dialysis patients, and are related to their CKD prognosis and life prognosis. Chronic inflammation and atherosclerotic disease are associated with malnutrition. Because malnutrition and its related factors affect their prognosis, it is necessary to find and treat patients with malnutrition at an early stage. The state in which the storage of protein and energy source accompanying CKD is decreased is called protein energy wasting (PEW). PEW is diagnosed on the basis of biochemical tests finding such as hypoalbuminemia, physique, muscle mass, and loss of dietary intake. For evaluating PEW, a complex nutritional index taking into account the pathophysiology specific to CKD patients is useful. Because PEW involves various factors such as nutritional status, muscular strength, ADL, and social life, the combined effect of various problems exacerbates PEW and affects life prognosis of CKD patients and dialysis patients. Taking these factors into consideration, not only nutritional therapy but also exercise therapy is necessary to stop the vicious cycle related to the decline of PEW and ADL.

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.

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.

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

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 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)

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

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

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

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.

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.

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.

Objective Parents of children with cancer are susceptible to psychological distress; however, many parents also report posttraumatic growth (PTG). The objective of this study was to explore the variables associated with PTG in parents of children with cancer who were either on treatment or off treatment. Methods One hundred and nineteen parents (71 mothers and 48 fathers) of children with cancer completed self-report questionnaires including the Posttraumatic Growth Inventory (PTGI), Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Inventory (STAI), and Impact of Event Scale-Revised (IES-R). Demographic data and children's medical information were also collected. Multivariate linear regression analyses were conducted to investigate the variables associated with PTG. Results The mean age of participants was 41.4 years (SD = 6). Higher PTGI scores were associated with parents’ lower trait anxiety (p = 0.028), parents’ sex (female) (p = 0.004), treatment status (within 12 months from treatment end compared with on-treatment) (p = 0.048), surgery (p = 0.007), and late effects (p = 0.01). Conclusions Parents’ PTG was associated with children's clinical characteristics, parents’ sex, and parents’ anxiety levels. When dealing with PTG, the parents’ psychological characteristics and children's clinical characteristics should be considered. Particularly for parents with high trait anxiety, it is important to reduce anxiety first before addressing PTG. This article is protected by copyright. All rights reserved.

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

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 (

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

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

BackgroundThe benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents.MethodsThis multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman’s rank-correlation coefficient.ResultsOf the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change − 0.6 ± 0.7%,P P P ρ = − 0.17,P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman’sρ = − 0.19,P = 0.011).ConclusionsDapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registrationUMIN-CTR: UMIN000016304

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.

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