Cigarette smoking and progression of kidney dysfunction: a longitudinal cohort study.

INTRODUCTION: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established. METHOD: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis. RESULTS: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001). CONCLUSION: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria.

Development of a prognostic risk score to predict early mortality in incident elderly Japanese hemodialysis patients.

BACKGROUND: Information of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients. MATERIALS AND METHODS: We analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study. RESULTS: Using the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (<20), yes = 2, no = 0; cancer, yes = 1, no = 0; dementia, yes = 3, no = 0; lower creatinine (<6.5 mg/dL), yes = 1, no = 0; lower albumin (<3.0 g/dL), yes = 3, no = 0; normal or high calcium (≥8.5 mg/dL), yes = 1, no = 0; and higher C reactive protein (>2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (p<0.001). CONCLUSION: We developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.

Association of secondhand smoke exposure and health-related lifestyle behaviors among male university employees in Japan.

Secondhand smoke (SHS) exposure causes various health problems associated with an unhealthy lifestyle. However, the lifestyles of individuals exposed to SHS have not been characterized extensively. Therefore, this cross-sectional study aimed to investigate the association between SHS exposure and lifestyle behaviors. The participants were 2379 healthy male employees at Osaka University who underwent health examinations. Physical and biochemical parameters and lifestyle behavior data were obtained from all the participants. Participants with SHS exposure had significantly higher body mass index, waist circumference, and serum levels of triglycerides and uric acid than that of those without SHS exposure. SHS exposure was significantly correlated with several lifestyle behaviors, including TV time, frequency of breakfast consumption and fried food consumption, vegetable and fruit intake, alcohol consumption frequency and daily alcohol intake, and smoking status. Thus, SHS exposure may be associated with an unhealthy lifestyle. The lifestyle behaviors of the smoke-excluded population were assessed further; however, SHS exposure was still associated with dietary and drinking habits. Since participants with SHS exposure are likely to have an unhealthy life and combined unhealthy lifestyle behaviors, the confounding effect of these factors should be considered when assessing the impact of SHS exposure on health.

The effect of lifestyle on the mortality associated with respiratory diseases in the general population.

Lifestyle factors, including smoking habit, diet, and physical activity, affect the prognosis of various diseases. We elucidated the effect of lifestyle factors and health status on deaths from respiratory diseases in the general Japanese population using data from a community health examination database. Data of the nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kenshin), targeting the general population in Japan, from 2008 to 2010 were analyzed. The underlying causes of death were coded according to the International Classification of Diseases (ICD)-10. The hazard ratios of the incidence of mortality associated with respiratory disease were estimated using the Cox regression model. This study included 664,926 participants aged 40-74 years, who were followed up for 7 years. There were 8051 deaths, including 1263 (15.69%) deaths from respiratory diseases. The independent risk factors of mortality associated with respiratory diseases were male sex, older age, low body mass index, no exercise habit, slow walking speed, no drinking habit, smoking history, history of cerebrovascular diseases, high hemoglobin A1c and uric acid levels, low low-density lipoprotein cholesterol level, and proteinuria. Aging and decline of physical activity are significant risk factors for mortality associated with respiratory diseases, regardless of the smoking status.

Soluble angiotensin-converting enzyme 2 association with lipid metabolism.

Increased expression of angiotensin-converting enzyme 2 (ACE2) is one of the likely explanations for disease severity in patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to test whether soluble ACE2 (sACE2) levels are correlated to known risk factors of severe COVID-19 including biochemical parameters, body mass index and smoking habits. We cross-sectionally evaluated serum sACE2 levels in obese or tobacco-smoking populations and compared them to those in non-obese and non-smoking healthy participants. Additionally, fibroblast growth factor-21 (FGF21) was investigated as a candidate regulator of sACE2. A total of 220 male participants aged 30-59 years undergoing an annual health checkup were enrolled in this study: 59 obese, 80 smokers, and 81 healthy. Serum sACE2 levels were significantly higher in obese participants but not in tobacco-smoking participants when compared to healthy participants. sACE2 levels were significantly correlated with total cholesterol and triglycerides but not with body mass index. Furthermore, no regulatory relationship was found between FGF21 and sACE2. Lipid metabolism disorders accompanied by upregulation of serum sACE2 may be underlying mechanisms of COVID-19 aggravation and might be a novel breakthrough treatment target.

Healthy Lifestyle and Incident Hypertension and Diabetes in Participants with and without Chronic Kidney Disease: The Japan Specific Health Checkups (J-SHC) Study.

Objective Whether or not combined lifestyle factors are associated with similar decreases in risks of incident hypertension and diabetes among individuals with and without chronic kidney disease (CKD) remains unclear. Methods This population-based prospective cohort study included participants 40-74 years old who were free from heart disease, stroke, renal failure, hypertension, diabetes, and hypercholesterolemia at baseline (n =60,234). Healthy lifestyle scores (HLSs) were calculated by adding the total number of 5 healthy lifestyle factors (non-smoking, body mass index <25 kg/m2, regular exercise, healthy eating habits, and moderate or less alcohol consumption). Cox proportional hazards models were used to examine associations between the HLS and incident hypertension or type 2 diabetes and whether or not CKD modified these associations. Results During a median of 4 years, there were 2,773 incident hypertension cases (30.1 cases per 1,000 person-years) and 263 incident diabetes cases (2.4 cases per 1,000 person-years). The risk of developing hypertension and diabetes decreased linearly as participants adhered to more HLS components. Compared with adhering to 0, 1, or 2 components, adherence to all 5 HLS components was associated with a nearly one-half reduction in the risk of hypertension [hazard ratio (HR) =0.52; 95% confidence interval (CI), 0.45-0.60] and diabetes (HR=0.51; 95% CI, 0.32-0.81) in fully adjusted models. CKD did not have a modifying effect on associations between the HLS and incident hypertension (Pinteraction=0.6) or diabetes (Pinteraction=0.3). Conclusion Adherence to HLS components was associated with reduced risks of incident hypertension and diabetes, regardless of CKD status.

Serum FGF21 levels are altered by various factors including lifestyle behaviors in male subjects.

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Trace proteinuria as a risk factor for cancer death in a general population.

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.

The distribution of eGFR by age in a community-based healthy population: the Japan specific health checkups study (J-SHC study).

BACKGROUND: 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. METHODS: 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 < 0.001). By sex, the distribution of eGFR and the 1-year change in eGFR showed similar results in both men and women. CONCLUSIONS: Renal function slowly declined with age in a healthy population; however, it was relatively preserved until the mid 70 s. This result suggests that a decline in renal function often observed in the elderly does not attribute to aging alone, and further examination might be required to clarify the cause of renal impairment.

One-year change in plasma volume and mortality in the Japanese general population: An observational cohort study.

BACKGROUND: Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population. METHODS AND RESULTS: We used a nationwide database of 134,291 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss-Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan-Meier analysis demonstrated that the highest 5th quintile had the greatest risk among the five groups. Multivariate Cox proportional hazard regression analysis demonstrated that a 1-year change in plasma volume was an independent risk factor for all-cause, cardiovascular, non-cardiovascular, and cancer deaths. The addition of a 1-year change in plasma volume to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes. CONCLUSIONS: Here, we have demonstrated for the first time that a 1-year change in plasma volume could be an additional risk factor for all-cause, cardiovascular, and non-cardiovascular (mainly cancer) mortality in the general population.

The Effect of CKD on Associations between Lifestyle Factors and All-cause, Cancer, and Cardiovascular Mortality: A Population-based Cohort Study.

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 <60 mL/min/1.73 m2, ≥1+ proteinuria on urinalysis, or both. The following lifestyle behaviors were considered healthy: no smoking, body mass index <25 kg/m2, moderate or lower alcohol consumption, regular exercise, and healthy eating habits. Healthy lifestyle scores were calculated by adding the total number of lifestyle factors for which each participant was at low risk. Cox proportional hazards models were used to examine associations between healthy lifestyle scores and all-cause, cancer, and cardiovascular mortality, and whether CKD modified these associations. Results During a median follow-up of 4.7 years, 3,471 participants died. The risks of all-cause and cancer mortality decreased as the number of five healthy lifestyle factors that were adhered to increased, irrespective of the CKD status. The risk of cardiovascular mortality, however, was modified by CKD (interaction p=0.07), and an unhealthy lifestyle and CKD synergistically increased cardiovascular mortality. Conclusion A healthy lifestyle can reduce the risk of all-cause and cancer death in patients with or without CKD, while the prevention of CKD is essential for reducing the risk of cardiovascular death.

Higher cardiovascular mortality in men with persistent dipstick hematuria.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: In men, persistent dipstick hematuria is a significantly risk factor of all-cause mortality, in particular cardiovascular death among general screening participants.

Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria.

BACKGROUND: Steroid therapy is one of the important therapies for IgA nephropathy (IgAN), but the features of the IgAN patients who have the benefit from this therapy remained unclear. METHODS: This retrospective observational study, using data of 874 patients with IgAN analyzed the proteinuria and kidney function of IgAN patients who had beneficial effect by steroid therapy. Two advantages of the present study were a large cohort and a long observational period. RESULTS: Corticosteroid therapy had ameliorated the kidney prognosis [incident rate ratio (IRR) 0.57 (95%CI 0.34-0.92), P = 0.029]. Because of interaction between kidney function and use of corticosteroid (P = 0.047), stratification analysis by kidney function revealed that prognosis of kidney function in IgAN patients whose eGFR was less than 60 ml/min/1.73m2 was ameliorated by corticosteroid therapy [IRR 0.50 (95%CI 0.26-0.97), P = 0.015); while, there was no change of kidney prognosis in IgAN patients whose eGFR was above 60 ml/min/1.73 m2. To make the target of corticosteroid therapy for IgAN patients more clear, IgAN patients, whose eGFR were less than 60 ml/min/1.73 m2, were stratified by proteinuria (1 g/day). In IgAN patients whose eGFR were under 60 ml/min/1.73 m2 and whose proteinuria were over 1.0 g/day, corticosteroid therapy seemed to ameliorate kidney function [IRR 0.39 (95%CI 0.19-0.86), P < 0.05]; while, there was obviously no change by corticosteroid therapy in IgAN patients whose eGFR were less than 60 ml/min/1.73 m2 and whose proteinuria were less than 1.0 g/day. CONCLUSION: Our results suggested that steroid therapy was especially effective for IgAN patients whose eGFR was less than 60 ml/min/1.73 m2 and whose proteinuria was more than 1.0 g/day.

Higher baseline uric acid concentration is associated with non-attainment of optimal blood pressure.

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<0.01), adjusted for potential confounders, such as age, sex, body mass index, presence of diabetes/dyslipidemia/chronic kidney disease (CKD), history of cardiovascular disease, daily drinking, and current smoking. In the subgroup analysis of female participants and participants with diabetes and CKD, a significant association was observed between +1 mg/dL of uric acid and NOBP. Higher uric acid concentration at baseline was significantly associated with NOBP on the first use of antihypertensive drug(s).

Impact of Metabolic Syndrome on the Mortality Rate among Participants in a Specific Health Check and Guidance Program in Japan.

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.

Intensive uric acid-lowering therapy in CKD patients: the protocol for a randomized controlled trial.

BACKGROUND: Hyperuricemia would be a risk factor for the development/progression of CKD. However, several studies showed U-shape association between serum uric acid level and renal impairment, suggesting that hypouricemia was rather associated with renal dysfunction. Perhaps, there is the optimal target level of serum UA for renal function. METHODS: The Target-UA study is a multicenter randomized controlled trial. Eligible CKD patients (eGFR ≥ 30, < 60 mL/min/1.73 m2 and urine protein < 0.5 g/gCr or urine albumin to creatinine ratio (ACR) < 300 mg/gCr) with serum UA ≥ 8.0 mg/dL (≥ 7.0 mg/dl: under the treatment) will be enrolled and be randomly assigned to the intensive therapy group (target serum UA level ≥ 4.0 mg/dL, < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL, < 7.0 mg/dL). Topiroxostat, a new xanthine oxidase inhibitor, will be administered to treat hyperuricemia. The primary endpoint is a change in logarithmic value of urine ACR between baseline and week 52 of treatment. The secondary endpoints include changes in serum UA, eGFR, urine protein, lipid profile, and onset of composite cardiovascular events, renal events, gouty arthritis, and attack of urolithiasis. The number of subjects has been set to be 185 in each group for a total of 370. DISCUSSION: This is the first study, to the best of our knowledge, to determine the optimal target level of serum UA for renal protection and is expected to lead to progress in CKD treatment. TRIAL REGISTRATION: (UMIN000026741 and jRCTs051180146).

Cause-specific mortality in the general population with transient dipstick-proteinuria.

Recently, changes in urinary albumin and in GFR have been recognized as risk factors for the development of end-stage kidney disease and mortality. Though most clinical epidemiology studies of chronic kidney disease (CKD) used renal function and proteinuria at baseline alone, definitive diagnosis of CKD with multiple measurements intensifies the differences in the risk for mortality between the CKD and non-CKD populations. We hypothesized that a transient diagnosis of proteinuria and reduced renal function each indicate a significantly higher mortality compared to definitive non-CKD as the negative control and lower mortality compared with definitive CKD as the positive control. The present longitudinal study evaluated a general-population cohort of 338,094 persons who received annual health checkups, with a median 4.3-year study period. There were 2,481 deaths, including 510 CVD deaths (20.6%) and 1,328 cancer deaths (53.5%), and mortality risk was evaluated for transient proteinuria and for transiently reduced renal function. The hazard ratios (HRs) for all-cause mortality and cancer mortality were not significant, but that for cardiovascular mortality was significantly higher for transient proteinuria (HR, 1.94 [95% confidence interval, 1.27-2.96] in men and 2.78 [1.50-5.16] in women). On the other hand, transiently reduced renal function was not significant for either cardiovascular mortality risk or cancer mortality risk. We surmise that this is the first study of the mortality risk of transient dipstick proteinuria in a large general-population cohort with cause-specific death registration. Transiently positive proteinuria appears to be a significant risk specifically for cardiovascular mortality compared with definitely negative for proteinuria.

Implication of alpha-Klotho as the predictive factor of stress.

Stress is known as a risk factor for both mental and physical health problems. While stress is known as one of the major health problems in modern society, a biomarker of stress has not yet been well established. In the present study, we focused on the serum levels of α-Klotho (αKl) as a possible objective biomarker of stress. Subjects included apparently healthy individuals who underwent a health examination in the Osaka University Health and Counseling Center. Physical and biochemical parameters were obtained from all subjects. Information regarding the lifestyle of each individual was obtained via questionnaires. Among male subjects, serum levels of soluble αKl (sαKl) were significantly elevated in subjects who had poor stress management and unsatisfactory sleep, suggesting that stress management and sleeping conditions influenced the serum levels of sαKl. The total Kessler Screening Scale for Psychological Distress (K6) score was significantly increased in subjects who reported experiencing considerable stress, had poor stress management and unsatisfactory sleep. Since serum levels of sαKl showed the same tendency as the K6 score in terms of the relationship between stress management and sleeping conditions in male subjects, increased sαKl levels could be associated with considerable psychological stress in healthy men.

Fast eating is a strong risk factor for new-onset diabetes among the Japanese general population.

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.

A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD.

BACKGROUND: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. METHODS: To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3-4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score. RESULTS: We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group's dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups. CONCLUSIONS: MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.