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Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear. The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years. Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI

Objective Results from previous studies on the dose-dependent effect of adhering to multiple lifestyle factors on all-cause mortality in patients with chronic kidney disease (CKD) are inconsistent, despite the reported dose-dependent effect in the general population. This study aimed to examine whether CKD modifies the dose-dependent effect of adhering to multiple lifestyle factors on mortality. Methods This population-based prospective cohort study targeted 262,011 men and women aged 40-74 years at baseline. Of these, 18.5% had CKD, which was defined as GFR

Background Patients treated with antihypertensive medication, even those with well controlled blood pressure (BP), are at higher risk for the development of atherosclerotic cardiovascular disease (ASCVD) in comparison to nonhypertensive individuals with optimal risk levels. We hypothesized that this residual risk could be stratified based on urinary albumin excretion (UAE). Methods A total of 13 082 middle-aged and older individuals with SBP/DBP of less than 160/100 mmHg and urinary albumin-to-creatinine ratios (UACRs) of less than 300 mg/g, and who were free from ASCVD events, were followed to investigate the incidence of ASCVD. The baseline BP was classified into four categories: normal BP (BP1), high normal BP (BP2), elevated BP (BP3), and grade 1 hypertension (BP4) based on the 2019 Japanese Society of Hypertension guidelines. Results After an average 10.6 ± 2.6 years of follow-up, the multivariable hazard ratio for the development of ASCVD (n = 994) was already increased in medicated hypertensive patients with BP1 in comparison with untreated individuals with BP1; however, among medicated hypertensive patients, this risk was separated between the UAE groups, which were classified according to the median UACR (male, 15.4 mg/g; female, 19.0 mg/g). In medicated hypertensive patients with any category of BP1-BP3, the adjusted risk of the development of ASCVD in those with lower and higher UACRs was comparable to that observed in untreated individuals in the BP1 and BP4 categories, respectively. Conclusion In medicated patients with well controlled hypertension, UAE is useful for stratifying the residual risk of developing ASCVD in comparison to nonhypertensive individuals with optimal risk levels.

Most data on chronic kidney disease (CKD) prevalence has been based on single measurements of renal function and proteinuria. The aim was to determine the prevalence of CKD diagnosed by chronic proteinuria and/or reduced eGFR in a recent year in Japan. In the main study, using a population-based cohort in Japan, the overall prevalence of CKD, defined as persistent positive proteinuria and/or eGFR

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25–1.49] and 1.69 [1.41–2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

Objective In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) program was started in 2008 to decrease the social burden related to metabolic syndrome (MetS). However, so far this program has not been found to have any impact on the mortality rate. Methods The subjects consisted of individuals who participated in the Tokutei-Kenshin in seven districts between 2008 and 2015. Using a National database of death certificates, we identified those who might have died and then further confirmed such deaths with the collaboration of the regional National Health Insurance agency and public health nurses. The diagnosis of MetS was made according to the Japanese criteria. The causes of death were classified by ICD-10. Mortality risk was evaluated after adjusting for age, sex, smoking, alcohol intake and past medical history such as stroke, heart disease and kidney disease. Results Among the total of 664,926 subjects, we identified 8,051 fatal cases by the end of 2015. The crude death rate was 1.6% for those with MetS, 1.3% for those with preliminary metabolic syndrome, and 1.1% those without MetS. In MetS, the adjusted hazard ratio (95% confidence interval) was 1.08 (1.02-1.15) for all-cause and 1.39 (1.22-1.58) for cardiovascular disease mortality when the reference was for those without MetS. Conclusion The death rate was found to be significantly higher among the participants with MetS.

International audience; Objective: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. Design and Methods: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study–participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. Conclusion: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Background and objective Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT. Design, setting, participants, and measurements We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5–9 and ≥10 medications per day, respectively. Results The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality. Conclusions The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

Inadequate blood pressure control is one of the important causes of chronic kidney disease (CKD), but only a limited number of reports have examined blood pressure control in Japanese patients with pre-dialysis CKD. Differences in blood pressure control due to underlying renal disease in pre-dialysis patients with CKD were investigated in the present study using the baseline data of the Fukushima CKD cohort study. The study involved 1351 CKD patients, classified by underlying disease of primary renal disease, hypertensive nephropathy, diabetic nephropathy, other nephropathies, or unknown. Target blood pressure of CKD patients was defined as

This longitudinal cohort study aimed to create a novel prediction model for cardiovascular death with lifestyle factors. Subjects aged 40–74 years in the Japanese nationwide Specific Health Checkup Database in 2008 were included. Subjects were randomly assigned to the derivation and validation cohorts by a 2:1 ratio. Points for the prediction model were determined using regression coefficients that were derived from the Cox proportional hazards model in the derivation cohort. Models 1 and 2 were developed using known risk factors and known factors with lifestyle factors, respectively. The models were validated by comparing Kaplan-Meier curves between the derivation and validation cohorts, and by calibration plots in the validation cohort. Among 295,297 subjects, data for 120,823 were available. There were 310 cardiovascular deaths during a mean follow-up of 3.6 years. Model 1 included known risk factors. In model 2, weight gain, exercise habit, gait speed, and drinking alcohol were additionally included as protective factors. Kaplan-Meier curves matched better between the derivation and validation cohorts in model 2, and model 2 was better calibrated. In conclusion, our prediction model with lifestyle factors improved the predictive ability for cardiovascular death.

Aims: The proper management of atherosclerotic risk factors (ARFs) and attainment of target levels (TLs) for ARFs are crucial in preventing atherosclerotic cardiovascular disease (ASCVD). In this study, utilizing data from the “Specific Health Check and Guidance in Japan,” which was conducted from 2008 to 2011, we examined TL attainment status of low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) and prescription status of dyslipidemia and hypertension in patients with diabetes undergoing medical treatment, and analyzed the factors that affected prescription status. Methods: Subjects receiving medical treatment for diabetes were selected from the database. Subjects were classified by prescription status for dyslipidemia and hypertension, and TL attainment status was assessed for each ARF. Results: The percentage of subjects who did not attain TLs and were not under medication was higher for LDL-C than for BP. The un-prescribed rates among non-TL-attained subjects were 60%–75% for LDL-C, and around 30%–40% for BP. The un-prescribed rates to those who were qualified for prescription therapy were also higher for LDL-C than for BP. Logistic regression analyses revealed that the subjects who were prescribed for dyslipidemia had the following characteristics compared with the un-prescribed non-TL-attained subjects: older age, higher body mass index, lower estimated glomerular filtration rate, previous heart or cerebrovascular disease, and higher medication rate for other ARFs. Conclusions: The present study revealed that, in Japan, the adequate prescription rate for dyslipidemia was lower than that for hypertension in patients with diabetes, suggesting the proper prescription therapy for dyslipidemia should be pursued to further prevent ASCVD.

Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as − (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03–1.31), 1.47 (1.27–1.70), and 1.61 (1.33–1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09–2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population.

Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m2 and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR 2 or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8–11.0) years. Kaplan–Meier survival analysis indicated that the risks of developing DKD, eGFR 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15–2.08) and proteinuria (HR 1.55, 95% CI 1.08–2.23), but not for an eGFR 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.

Dipstick urine tests are a simple and inexpensive method for detecting kidney and urological diseases, such as IgA nephropathy and bladder cancer. The nationwide mass screening program, Specific Health Checkup (SHC), started in Japan in 2008 and targeted all adults between 40 and 74 years of age. Dipstick urine tests for proteinuria and glucosuria are mandatory as part of the SHC, but dipstick urine tests for hematuria are not. However, the dipstick hematuria test is often administered simultaneously with these mandatory tests by some health insurers. Hematuria is common in Japanese general screening participants, particularly elderly women, and the necessity of mass screening using the dipstick hematuria test has been discussed. This study aimed to evaluate the cost-effectiveness of mass screening for dipstick hematuria tests in addition to the SHC.Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from a Japanese societal perspective.Compared with the current SHC, mass screening for dipstick hematuria tests, in addition to the SHC, costs less and gains more, which means cost-saving. Similar findings were observed in the sex-specific analysis.Our results suggest that mandating the dipstick hematuria test could be justifiable as an efficient use of finite healthcare resources. The results have implications for mass screening programs not only in Japan but worldwide.

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Renal function gradually declines with age. However, the association between changes in renal function and healthy aging has not been determined. This study examined the distribution of estimated glomerular filtration rate (eGFR) values in healthy subjects by age using large-scale cross-sectional data of health check-up participants in Japan. Among the 394,180 health check-up participants, 75,217 (19.1%) subjects without hypertension, diabetes, hyperlipidemia, obesity, proteinuria, smoking, past history of cardiovascular diseases, and renal failure/not undergoing dialysis were included in the healthy group. The distribution of eGFR values was determined at each age between 39 and 74 years. Results: in healthy subjects, the mean (± 2 SD range) values of eGFR (mL/min/1.73 m2) at ages 40, 50, 60, and 70 were 88.0 (55.4–121.7), 82.3 (51.2–113.3), 77.8 (48.1–107.6), and 72.9 (44.7–101.1), respectively. The difference in the mean eGFR by age was almost constant across all ages. In the linear regression analysis adjusted for sex, the regression coefficient of mean eGFR for a one-year increase in age was -0.46 mL/min/1.73 m2 in healthy subjects (P

As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial.The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease.Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia ( 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4 mmol/L. Compared with a reference level of 4.0-4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium 4.0 mmol/L, 1.72 (1.00-2.96) for 4.5-4.9 mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment.Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.

Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm rupture remain fatal with extremely high mortality rates. Owing to the relatively low prevalence of AD, the risk of AD-related death has not yet been elucidated. The aim of the present study was to examine whether hyperuricemia is a risk factor for AD-related mortality in the general population. We used a nationwide database of 474,725 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” between 2008 and 2013. There were 115 deaths from aortic dissection and aortic aneurysm rupture during the follow-up period of 1,803,955 person-years. Kaplan–Meier analysis revealed that subjects with hyperuricemia had a higher rate of AD-related death than those without hyperuricemia. Multivariate Cox proportional hazard regression analysis demonstrated that hyperuricemia was an independent risk factor for AD-related death in the general population. The net reclassification index was improved by addition of hyperuricemia to the baseline model. This is the first report to demonstrate that hyperuricemia is a risk factor for AD-related death, indicating that hyperuricemia could be a crucial risk for AD-related death in the general population.

We previously reported that dipstick hematuria (UH) was associated with higher all-cause mortality in men, but not in women. We extended the observation and examined the causes of death using repeated urinalysis in men. Subjects were those who participated the Tokutei–Kenshin between 2008 to 2015 in seven districts. Using National database of death certificate, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. Dipstick results of 1 + and higher were defined as hematuria. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazard analysis. We adjusted for age, body mass index, eGFR, proteinuria, comorbid condition (diabetes mellitus, hypertension, and dyslipidemia), past history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise). A total of 170,119 men were studied and 70,350 (41.4% of the total) were re-examined next year. The prevalence of UH (−/−), UH (−/+), UH (±), and UH (+ /+) was 77.2% (N = 54,298), 14.0% (N = 9,838), 1.4% (N = 1014) and 7.4% (N = 5,200), respectively. We identified 1,162 deaths (1.7% of the total of the re-examined). The adjusted HR (95% CI) was 1.49 (1.22–1.81) for all-cause mortality and 1.83 (1.23–2.71) for cardiovascular death compared to those with UH (−/−), respectively. However, that for cancer mortality risk was not significant: 1.23 (0.92–1.64). In men, persistent dipstick hematuria is a significantly risk factor of all-cause mortality, in particular cardiovascular death among general screening participants.

The Framingham Risk Score (FRS) has been reported to predict coronary heart disease (CHD), but its assessment has been unsuccessful in Asian population. We aimed to assess FRS and Suita score (a Japanese CHD prediction model) in a Japanese nation-wide annual health check program, participants aged 40–79 years were followed up longitudinally from 2008 to 2011. Of 35,379 participants analyzed, 1,234 had new-onset CHD. New-onset CHD was observed in diabetic men [6.00%], non-diabetic men [3.96%], diabetic women [5.51%], and non-diabetic women [2.86%], respectively. Area under the curve (AUC) of receiver operating characteristic (ROC) curve for CHD prediction were consistently low in Suita score (TC), FRS (TC) and NCEP-ATPIII FRS (TC), suggesting that these scores have only a limited power. ROC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) and Hosmer–Lemeshow goodness-of-fit test did not show clear differences between Suita score (TC) and FRS (TC). New models combining waist circumference ≥85 cm in men or proteinuria ≥1+ in women to Suita score (TC) was superior in diabetic men and women. New models could be useful to predict 3-year risk of CHD at least in Japanese population especially in diabetic population.

Pneumonia-related mortality is expected to increase in aging societies. This prospective cohort study examined whether daily walking (1 hour/day) could reduce pneumonia-related mortality among older people who lacked other exercise habits. We analysed data from Japanese Specific Health Checkup across 82 municipalities in 7 prefectures among participants aged ≥65 years who participated in daily walking but did not regularly engage in other forms of exercise (n = 132,448). Information on walking habits and health-related indicators was assessed at a baseline survey conducted between 2008 and 2014. Pneumonia-related and all-cause mortality were followed for a median of 3.4 years. We performed a competing risk model with propensity score matching to evaluate the association between daily walking habits and pneumonia-related mortality. Our propensity-matched analysis revealed a significant association between daily walking and pneumonia-related mortality among older people who lacked other exercise habits, such that the sub-hazard ratio and 95% confidence intervals were 0.58 (0.39, 0.86). This study extends the findings of previous research on the effects of exercise on pneumonia by demonstrating that daily walking alone is sufficient to reduce pneumonia-related mortality among older people who do not regularly engage in other exercise habits.

Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP p for trend 0.02) only in those without BP meds. Conclusion: Lower DBP was associated with higher risk of incident CKD only in the general population taking antihypertensive medication.

BACKGROUND Our aim was to assess how the population-attributable fraction (PAF) for premature mortality due to cardiovascular disease (CVD) associated with hypertension changes if blood pressure (BP) thresholds for hypertension were lowered from systolic/diastolic BP ≥140/90 mm Hg to ≥130/80 mm Hg, as defined using the 2017 American College of Cardiology/American Heart Association blood pressure guideline. METHODS Analyses were conducted using a database of participants who underwent a national health checkup examination started in 2008 in Japan (n = 510,238; mean age, 59.6 ± 8.1 years; 42% men). Each participant was categorized as having normal or elevated BP, or stage 1 or 2 hypertension according to the guideline. Data on premature mortality due to CVD occurring before age 70 years were available through March 2015. RESULTS Over a median follow-up of 3.4 years, 739 deaths from CVD occurred. After multivariable adjustment, hazard ratios for premature CVD mortality for elevated BP, stage 1 hypertension, and stage 2 hypertension vs. normal BP were 1.02 (95% confidence interval, 0.72, 1.44), 1.33 (1.02, 1.75), and 2.41 (1.90, 3.05), respectively. The PAF associated with stage 1 and 2 hypertension was 4.4% and 39.4%, respectively. CONCLUSIONS In the current nationwide study of Japanese adults, stage 1 and 2 hypertension were associated with an increased risk for premature CVD mortality. The PAF for premature CVD mortality associated with hypertension increased by 4.4% if BP thresholds for hypertension were lowered from systolic/diastolic BP ≥140/90 to ≥130/80 mm Hg.

Background Aortic artery disease (AAD), such as aortic dissection or aortic aneurysm rupture, is fatal, with an extremely high mortality. Because of its low incidence, the risk for the development of AAD has not yet been elucidated. Hypertension (HT) is an established risk factor for cardiovascular disease, but there has been no prospective study on the effect of HT on AAD-related mortality. Methods and Results: We used a nationwide database of 276,197 subjects (aged 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" from 2008 to 2010. There were 80 AAD-related deaths during the follow-up period of 1,049,549 person-years. On multivariate Cox proportional hazard regression, HT was an independent risk factor for AAD-related death in apparently healthy subjects. On receiver operating characteristics curve analysis for AAD-related death, abnormal systolic and diastolic blood pressure (SBP and DBP) were 130 mmHg and 82 mmHg, respectively. The prediction capacity was significantly improved by the addition of SBP to confounding risk factors. Notably, further improvement of the C index was observed by addition of DBP to the model with SBP. Conclusions This is the first report to prospectively show that HT is a risk factor for AAD-related death. Both SBP and DBP are of critical importance in the primary prevention of AAD-related death in apparently healthy subjects.

Previous studies report conflicting results of a dose-dependent association between alcohol consumption and incidence of chronic kidney disease. Only a few studies have assessed the clinical impact of > 45–65 g/day of critically high alcohol consumption. This retrospective cohort study included 88,647 males and 88,925 females with dipstick urinary protein ≤ ± and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 at their first annual health examinations between April 2008 and March 2010 in Japan. The exposure was the self-reported alcohol consumption. The outcome was proteinuria defined as dipstick urinary protein ≥ 1 + or ≥ 2 +. During median 1.8 years (interquartile range 1.0–2.1) of the observational period, 5416 (6.1%) males and 3262 (3.7%) females developed proteinuria defined as dipstick urinary protein ≥ 1 +. In males, a U-shape association between alcohol consumption and proteinuria was observed in a multivariable-adjusted Poisson regression model [incidence rate ratio (95% confidence interval) of rare, occasional, and daily drinkers with ≤ 19, 20–39, 40–59, and ≥ 60 g/day: 1.00 (reference), 0.86 (0.79–0.94), 0.70 (0.64–0.78), 0.82 (0.75–0.90), 1.00 (0.90–1.11), and 1.00 (0.85–1.17), respectively], whereas a J-shape association was observed in females [1.00 (reference), 0.81 (0.75–0.87), 0.74 (0.64–0.85), 0.93 (0.78–1.11), 1.09 (0.83–1.44), and 1.45 (1.02–2.08), respectively]. Similar associations with dipstick urinary protein ≥ 2 + were shown in males and females. Moderate alcohol consumption was associated with lower risk of proteinuria in both males and females. Females with ≥ 60 g/day of high alcohol consumption were at higher risk of proteinuria, whereas males were not. Females were more vulnerable to high alcohol consumption, than males.

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40–69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of &lt, 2 cups/week, those with an intake of 7 to &lt, 12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors, the HR (95% CI) was 0.53 (0.32–0.88). No significant associations were found in men. This study suggested that milk intake of 7 to &lt, 12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to &lt, 2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake.

Objective The association of serum triglycerides (TGs) and alcohol consumption with chronic kidney disease (CKD) is unclear. The purpose of this study was to investigate the association of serum TG and daily alcohol consumption with CKD in the general population. Design The design of the study was longitudinal cohort study. Subjects Male (n = 47,737) and female (n = 69,542) participants were grouped into quartiles based on serum TG levels. Main Outcome Measures We examined the associations of serum TG with annual changes in estimated glomerular filtration rate (eGFR) in all participants, the incident CKD in participants without CKD, and the progression of CKD in participants with CKD. We also examined the association of alcohol consumption with these factors and whether daily alcohol consumption alters the association of serum TG with renal prognosis. Results The higher quartile of serum TG at baseline was significantly associated with a greater decline in eGFR during the 2-year study period in all participants, even after adjustment for confounding factors. Serum TG was also significantly associated with the incidence and progression of CKD after 2 years in participants with and without CKD at baseline, respectively. Moreover, daily alcohol consumption was protectively associated with these outcomes. Stratified analysis according to the alcohol consumption status revealed that daily alcohol consumption modified the association of high TG with eGFR and CKD. Conclusion(s) Elevated serum TG was associated with the decline in eGFR and the incidence and progression of CKD. In addition, these associations were modified by daily alcohol consumption in this Japanese population.

A significant relationship exists between elevated uric acid concentration and both prevalent and incident hypertension; however, data regarding the influence of higher uric acid concentration at baseline on blood pressure control by antihypertensive drugs is scarce. Thus, a prospective cohort study was performed. The study outcome was the non-attainment of optimal blood pressure (NOBP). NOBP level was defined according to the Japanese hypertension guideline. This study enrolled a Japanese community-based cohort (N = 8,664; age 65.5 ± 6.4 years; women, 55.0%) who were not using antihypertensive drugs on the first visit for a health check-up program but started using antihypertensive drug(s) on the next-year visit. The participants were classified into quartiles based basic uric acid concentration. Odds ratios (ORs) were calculated for NOBP as the primary outcome measure. Multivariable logistic analysis showed that quartile 4 was significantly associated with NOBP when quartile 1 was set as the reference (OR (95% confidence interval), 1.36 (1.16-1.59), p

Several recent clinical trials and meta-analyses have shown that lowering blood pressure reduces the risk of cardiovascular disease. However, current evidence that describes general demographics in blood pressure and mortality with chronic kidney disease is sparse in Japan. Using a population-based longitudinal cohort that received annual health checkups in Japan in 2008, hypertensive status, self-reported use of antihypertensive drugs, and prognosis were examined through 2012. Chronic kidney disease was defined as positive proteinuria or estimated glomerular filtration rate

Hyperuricemia is associated with all-cause and cardiovascular mortality. However, the threshold value of serum uric acid levels for increased risk of mortality has not been determined. This large-scale cohort study used a nationwide database of 500,511 Japanese subjects (40–74 years) who participated in the annual health checkup and were followed up for 7 years. The association of serum uric acid levels at baseline with cardiovascular and all-cause mortality was examined. The Cox proportional hazard model analysis with adjustment for possible confounders revealed that the all-cause and cardiovascular mortality showed a J-shaped association with serum uric acid levels at baseline in both men and women. A significant increase in the hazard ratio for all-cause mortality was noted with serum uric acid levels ≥ 7 mg/dL in men and ≥ 5 mg/dL in women. A similar trend was observed for cardiovascular mortality. This study disclosed that even a slight increase in serum uric acid levels was an independent risk factor for all-cause and cardiovascular mortality in both men and women in a community-based population. Moreover, the threshold values of uric acid for mortality might be different for men and women.

Although many studies that have examined the relationship of type and amount of food and the frequency of eating with new onset of diabetes, there are few reports on the relationship between how meals are eaten, such as skipping breakfast, snacking or food ingestion speed, and the onset of diabetes. We investigated the relationship between eating speed, as well as other eating habits such as snacking and skip breakfast, and new onset of diabetes in a nation-wide Japanese cohort. We obtained data from the nation-wide annual health check program in Japan. In 197,825 participants without diabetes in 2008, questionnaires recorded data on the diet habits (eating speed, snack after supper or before sleep, and skipping breakfast) and unadjusted and multivariable-adjusted logistic regression models were used to measure the odds ratio of new-onset diabetes mellitus in a 3-year follow up. The proportion of fast eaters, those who snack after supper, snack before sleep, and skip breakfast was higher in the new-onset diabetes group than in the group who did not develop diabetes mellitus. As compared with the non-fast eater group, fast eaters were generally younger, had higher BMI, had more weight gain from 20 years onwards, and experienced frequent weight fluctuations of ≥3 kg within 1 year. The risk of fast eaters developing diabetes mellitus remained even after correction for multiple factors including age, body weight, rate of weight change, blood pressure, smoking, and alcohol consumption. No other eating habits were independent predictors for onset of diabetes mellitus. Results show that fast eating is a sole predisposing factor among eating habits for new-onset diabetes. Future studies were warranted to evaluate whether avoidance of fast eating is beneficial for prevention of diabetes mellitus.

Chronic kidney disease (CKD) is characterized by a reduced glomerular filtration rate (GFR) and proteinuria. Modifiable lifestyle factors such as smoking and alcohol contribute to CKD. Recent cohort studies have shown that moderate alcohol consumption attenuates the decline of the GFR and smoking has been previously shown to be associated with CKD. However, the association of smoking and alcohol consumption on CKD is not entirely clear. To examine whether there is evidence to assume that smoking is an effective modifier of the association between CKD and alcohol consumption, we conducted a cross-sectional study of a population of people who presented for a health checkup under a program that targets the insured population aged ≧40 years using data from the Specific Health Check and Guidance in Japan between April 2008 and March 2009. Of the 506 807 participants aged ⩾40 years, 292 013 (57.6%) were included in the present analysis. Outcomes were kidney dysfunction, as an eGFR of

BackgroundPlasma volume status (PVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular disease because of its role in the prevention and of the management of heart failure. However, it remains undetermined whether an abnormal PVS is a risk for all-cause and cardiovascular mortality in the general population.Methods and resultsWe used a nationwide database of 230,882 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up between 2008 and 2011. There were 586 cardiovascular deaths, 2,552 non-cardiovascular deaths, and 3,138 all-cause deaths during the follow-up period of four years. Abnormally high and low PVS were identified from the results of 80% of all subjects (high and low PVS ≥ 7 and < -13.3, respectively). Multivariate Cox proportional hazard regression analysis demonstrated that high PVS was an independent risk factor for all-cause, cardiovascular and non-cardiovascular deaths. Although low PVS was a positive risk factor for cardiovascular deaths as well, it was a negative risk factor for non-cardiovascular deaths. The addition of PVS to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes.ConclusionsThis is the first prospective report to reveal the impact of PVS on all-cause and cardiovascular mortality. PVS could be an additional risk factor for all-cause and cardiovascular mortality in the general population.

Background and objectives Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes. Design, setting, participants, & measurements Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3–5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from “not at all” to “extremely.” Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life. Results Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval [95% CI], −4.6 to −2.3) and 2.3 (95% CI, −3.2 to −1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus. Conclusions Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.

Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate SBP (per 5 mmHg), SD DBP (per 3 mmHg), average real variability SBP (per 6 mmHg), and average real variability DBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11–1.20], 1.08 [1.04–1.12], 1.13 [1.09–1.17], 1.06 [1.02–1.10], respectively; all P BP and average real variability BP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06–1.15; all P

Although fasting plasma glucose levels

Dipstick urine tests are used for general health screening in Japan, but how the test results (e.g., glucosuria) relate to mortality is unknown.Subjects participated in a nationwide screening in 2008 in six districts in Japan. We identified those who might have died using the national database of death certificates from 2008 to 2012 (total registered ~ 6 million) and verified candidates with the regional National Health Insurance Agency and public health nurses. Diabetes mellitus (DM) was defined as HbA1c ≥ 6.5%, fasting blood glucose ≥ 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was defined as dipstick ≥ 1 +.Among 209,060 subjects, we identified 2714 fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for those without glucosuria and 3.4% for those with glucosuria. After adjusting for sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia), history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was 1.475 (1.166-1.849, P 0.001). DM subjects with glucosuria (N = 4655) had a higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N = 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511 (1.539-3.833, P 0.001)] than non-DM subjects without glucosuria (N = 183,690).Dipstick glucosuria significantly affected mortality in Japanese community-based screening participants.

Dipstick proteinuria, but not albuminuria, is used for general health screening in Japan. How the results of dipstick proteinuria tests correlate with mortality and, however, is not known. Subjects were participants of the 2008 Tokutei-Kenshin (Specific Health Check and Guidance program) in six districts in Japan. On the basis of the national database of death certificates from 2008 to 2012, we used a personal identifier in two computer registries to identify participants who might have died. The hazard ratio (95% confidence interval, CI) was calculated by Cox-proportional hazard analysis. Among a total of 140,761 subjects, we identified 1641 mortalities that occurred by the end of 2012. The crude mortality rates were 1.1% for subjects who were proteinuria (−), 1.5% for those with proteinuria (+/−), 2.0% for those with proteinuria (1+), 3.5% for those with proteinuria (2+), and 3.7% for those with proteinuria (≥ 3+). After adjusting for sex, age, body mass index, estimated glomerular filtration rate, comorbid condition, past history, and lifestyle, the hazard ratio (95% CI) for dipstick proteinuria was 1.262 (1.079–1.467) for those with proteinuria (+/−), 1.437 (1.168–1.748) for those with proteinuria (1+), 2.201 (1.688–2.867) for those with proteinuria (2+), and 2.222 (1.418–3.301) for those with proteinuria (≥ 3+) compared with the reference of proteinuria (−). Dipstick proteinuria is an independent predictor of death among Japanese community-based screening participants.

Anemia is common in chronic kidney disease (CKD) and may be associated with mortality in CKD patients. However, few studies have examined this relationship in Asian populations. A total of 62,931 Japanese people (age 64.0 ± 8.0 years; men 38.5%) were followed up from 2008 to 2012. Participants were divided into six groups in accordance with their estimated glomerular filtration rate (eGFR) (

Objective This study aimed to examine the association between the changes in an overall healthy lifestyle, as quantified by the number of unhealthy lifestyle factors and obesity status, and the incidence of proteinuria in the general Japanese population. Methods A retrospective cohort study was conducted among 99,404 (men, 36.9%) participants aged from 40-74 years of age who underwent two health check-ups with a 1-year interval in Japan between 2008 and 2009. Any participants with chronic kidney disease at baseline were excluded. The smoking status, body mass index, physical activity, alcohol consumption, and healthy eating habits were combined into a simple overall healthy lifestyle score ranging from 0 to 5. The changes in overall healthy lifestyle scores from baseline (range, -5 to +5) and the incidence of proteinuria, defined by a dipstick urinalysis (score ≥1+), were assessed at the second check-up. A logistic regression analysis was used to examine the association between the changes in overall healthy lifestyle scores and the incidence of proteinuria. Results After one year of follow-up, 3.9% of men and 2.4% of women developed proteinuria. Each increase (or decrease) in the changes in overall healthy lifestyle scores was associated with a reduced (or increased) risk of proteinuria in both men (odds ratio (OR) 0.87; 95% confidence interval (CI), 0.81-0.94) and women (OR 0.87; 95%CI, 0.80-0.94) after adjusting for age, baseline lifestyle scores, hypertension, diabetes mellitus, and hypercholesterolemia. Stratified analyses based on age, the presence or absence of hypertension, or diabetes mellitus revealed similar results. Conclusion Overall lifestyle changes, even within a year, were found to influence the incidence of proteinuria.

Background While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship. Methods This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. Results During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p

It is not known if urine dipstick alone can identify chronic kidney disease (CKD) in the general Japanese population. We designed a cross-sectional study using data obtained in 2008 from a nationwide community-based health examination program for adults aged 40–74. The data consisted of blood tests, urine tests and questionnaire related to metabolic disorders. Those who had both serum creatinine measured and urine dipstick tested were analyzed. Data were obtained from 538,846 people with a mean age of 62.8 years, consisting of 41.6 % males. Our study showed that 14.4 % had an eGFR below 60 mL/min/1.73 m2, 5.2 % had proteinuria and 18.1 % had CKD. Within the population with CKD, non-proteinuric CKD accounted for 71.4 %. The proportion of non-proteinuric CKD was highest in stage G3a (91.8 %) followed by G3b (77.0 %) disease, and was greater in the more elderly and in females. The proportion of non-proteinuric CKD was 47.9 % in diabetes mellitus, 69.3 % in dyslipidemia, 66.8 % in hypertension and 57.1 % in metabolic syndrome. Furthermore, non-proteinuric CKD accounted for 78.1 % of the population without these lifestyle diseases, suggesting that even in the population without apparent risk, CKD is still prevalent and can be missed when urine dipstick is the only screening method used. This study showed that a considerable population of CKD might be overlooked when only dipstick proteinuria is assessed for CKD screening. Hence, we strongly recommend that both urinalysis and serum creatinine measurement should be a part of the nationwide CKD screening system.

Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population.We used a nationwide database of 165 847 subjects (aged 29-74, male 40%) who participated in the annual 'Specific Health Check and Guidance in Japan' checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation.After adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR60 mL/min/1.73 m(2)) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption.This study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population.

To investigate how changes in eGFR can affect medical costs, a regional cohort of national health insurance beneficiaries in Japan was developed from a nationwide database system (Kokuho database, KDB), and non-individualized data were obtained. From 105,661 people, subjects on chronic dialysis and subjects without consecutive medical checkups were excluded. Finally, medical costs in the follow-up year categorized by annual changes in eGFR between baseline and the next year were longitudinally examined in 70,627 people ranging in age from 40 to 74 years. Global mean costs for subjects with a rapid decrease in eGFR (≤-30%/year) were the highest among all ΔeGFR categories. In men, the cost was 1.42 times that for a stable eGFR. A total of 6,268 (19.4%) men and 5,381 (14.0%) women with eGFR

To investigate the relationship between triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) and chronic kidney disease (CKD).We used data from 216,007 Japanese adults who participated in a nationwide health checkup program. Men (n = 88,516) and women (n = 127,491) were grouped into quartiles based on their TG/HDL-C levels (1.26, 1.26-1.98, 1.99-3.18, and3.18 in men;0.96, 0.96-1.44, 1.45-2.22, and2.22 in women). We cross-sectionally assessed the association of TG/HDL-C levels with CKD [defined as an estimated glomerular filtration rate (eGFR) of60 mL/min/1.73 m(2) (low eGFR) and/or proteinuria (defined as urinary protein ≥ 1+ on dipstick testing)], low eGFR, and proteinuria.The prevalence of CKD, low eGFR, and proteinuria increased significantly with elevating quartiles of TG/HDL-C in both genders (all P for trend0.001). Participants in the highest quartile of TG/HDL-C had a significantly greater risk of CKD than those in the lowest quartile after adjustment for the relevant confounding factors (odds ratio: 1.57, 95% confidence interval: 1.49-1.65 in men; 1.41, 1.34-1.48 in women, respectively). Furthermore, there were significant associations with low eGFR and proteinuria. In stratified analysis, the risk of CKD increased linearly with greater TG/HDL-C levels in participants with and without hypertension, diabetes, and obesity. Moreover, higher TG/HDL-C levels were relevant for CKD, especially in participants with hypertension and diabetes (P for interaction0.001, respectively).An elevated TG/HDL-C is associated with the risk of CKD in the Japanese population.

Background Our recently published cost-effectiveness study on chronic kidney disease mass screening test in Japan evaluated the use of dipstick test, serum creatinine (Cr) assay or both in specific health checkup (SHC). Mandating the use of serum Cr assay additionally, or the continuation of current policy mandating dipstick test only was found cost-effective. This study aims to examine the affordability of previously suggested reforms. Methods Budget impact analysis was conducted assuming the economic model would be good for 15 years and applying a population projection. Costs expended by social insurers without discounting were counted as budgets. Results Annual budget impacts of mass screening compared with do-nothing scenario were calculated as ¥79–¥−1,067 million for dipstick test only, ¥2,505–¥9,235 million for serum Cr assay only and ¥2,517–¥9,251 million for the use of both during a 15-year period. Annual budget impacts associated with the reforms were calculated as ¥975–¥4,129 million for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥963–¥4,113 million for mandating serum Cr assay only and abandoning dipstick test. Conclusions Estimated values associated with the reform from ¥963–¥4,129 million per year over 15 years are considerable amounts of money under limited resources. The most impressive finding of this study is the decreasing additional expenditures in dipstick test only scenario. This suggests that current policy which mandates dipstick test only would contain medical care expenditure.

The association between alcohol consumption and chronic kidney disease (CKD), characterized by reduced glomerular filtration rate and proteinuria, is controversial. Recent studies suggest that serum γ-glutamyltransferase (GGT) level, a conventional marker of excessive alcohol consumption, predicts the CKD incidence. Little information is available on the difference in the clinical impact of alcohol consumption and GGT on proteinuria.The present cross-sectional survey included 332,296 Japanese people aged ≥40 years in 2008. To examine the associations of GGT and alcohol consumption with proteinuria, 134,600 men and 197,696 women were classified into 20 categories based on GGT quartiles and alcohol consumption categories, and their prevalence rate ratios (PRR) of proteinuria defined as ≥1+ of dipstick urinary protein were calculated after adjusting for clinically relevant factors.Prevalence of proteinuria was 7.5 and 3.7 % in men and women, respectively. In both gender an association between alcohol consumption and proteinuria was in a J-shaped fashion with the lowest PRR of mild drinkers with ≤19 g/day of ethanol consumption, whereas an association between serum GGT level and proteinuria was linear. Compared with rare drinkers in the lowest GGT quartile, the subjects in higher GGT quartiles had a higher probability of proteinuria, irrespective of alcohol consumption. An optimal cutoff level of serum GGT was 43.6 and 23.2 IU/L in men and women, respectively.The subjects with higher serum GGT level had a higher probability of proteinuria, regardless of alcohol consumption, suggesting that GGT has a clinically greater impact on CKD than alcohol consumption.

A major earthquake measuring 9.0 on the Richter scale struck northeastern Japan at 2:46 pm on 11 March 2011. Several reports have described transient increases in blood pressure after major earthquakes, but the impact of such increases on hemodialysis patients has not been reported. We retrospectively investigated changes in blood pressure and influencing factors in 205 patients (mean age 66.6±13.0 years; male 51.7%; median dialysis vintage 6.0 (2.0–11.0) years) on chronic dialysis at three dialysis centers in the affected area (Fukushima City) for 8 weeks after the earthquake. Pre-dialysis blood pressure was significantly elevated at 1 week after the earthquake compared with baseline (systolic vs. diastolic blood pressure: 153.1±20.2/80.1±13.5 vs. 148.6±20.0/77.5±12.8 mm Hg, P