The Relationship of Alcohol Consumption and Drinking Pattern to the Risk of Glomerular Hyperfiltration in Middle-aged Japanese Men: The Kansai Healthcare Study.

BACKGROUND: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals. METHODS: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the entire cohort. RESULTS: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively. CONCLUSION: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.

Body Mass Index and the Risk of Persistent Proteinuria in Middle-Aged Men: The Kansai Healthcare Study.

INTRODUCTION: Proteinuria is a risk factor for end-stage renal failure. However, it is not known whether body mass index (BMI) is prospectively associated with the risk of future developing proteinuria, taking into account transient proteinuria. METHODS: We enrolled 9,320 nondiabetic Japanese middle-aged men who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive medications at baseline. "Any proteinuria" was defined as proteinuria detected for the first time during the follow-up period regardless of its frequency. "Persistent proteinuria" was defined as proteinuria that was detected at least twice consecutively at annual examinations and did not return to negative until the end of the follow-up. RESULTS: During the 11-year follow-up period, 1,972 cases of any proteinuria and 151 cases of persistent proteinuria were confirmed. Both lower and higher BMI were associated with the risk of any proteinuria. As for persistent proteinuria, in those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria. The association between BMI and the risk of persistent proteinuria was stronger than that between BMI and any proteinuria. In multiple-adjusted model, hazard ratios of persistent proteinuria for BMI <18.0, 18.0-19.9, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, and ≥28.0 kg/m2 were 1.52 (95% confidence interval 0.51-4.49), 1.07 (0.49-2.29), 1.00 (reference), 1.14 (0.64-2.01), 1.89 (1.09-3.27), 2.12 (1.15-3.93), and 3.85 (2.03-7.30), respectively. DISCUSSION/CONCLUSION: In those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria and any proteinuria. This relationship was stronger for persistent proteinuria than for any proteinuria.

Serum Gamma-Glutamyltransferase, Daily Alcohol Consumption, and the Risk of Chronic Kidney Disease: The Kansai Healthcare Study.

BACKGROUND: Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR). METHODS: We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR. CONCLUSION: In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease.

BACKGROUND: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. METHODS: A prospective cohort study of 9,116 middle-aged nondiabetic -Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1-23.0 g ethanol/day), moderate drinkers (23.1-46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. RESULTS: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11-1.70), 1.58 (95% CI 1.28-1.95), 2.27 (95% CI 1.86-2.77), and 3.12 (95% CI 2.56-3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46-0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. CONCLUSIONS: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.

The Association Between Metabolically Healthy Obesity and the Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Metabolically healthy obesity seems to be a unique phenotype for the risk of cardiometabolic diseases. However, it is not known whether this phenotype is associated with the risk of proteinuria. METHODS: Study subjects were 9,185 non-diabetic Japanese male workers aged 40-55 years who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive or lipid-lowering medications at baseline. Obesity was defined as body mass index ≥25.0 kg/m2. Metabolic health was defined as the presence of no Adult Treatment Panel III components of the metabolic syndrome criteria, excluding waist circumference, and metabolic unhealth was defined as the presence of one or more metabolic syndrome components, excluding waist circumference. "Consecutive proteinuria" was considered positive if proteinuria was detected twice consecutively as 1+ or higher on urine dipstick at annual examinations to exclude chance proteinuria as much as possible. RESULTS: During the 81,660 person-years follow-up period, we confirmed 390 cases of consecutive proteinuria. Compared with metabolically healthy non-obesity, metabolically healthy obesity was not associated with the risk of consecutive proteinuria (multiple-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.37-1.99), but metabolically unhealthy non-obesity with ≥2 metabolic syndrome components (HR 1.77; 95% CI, 1.30-2.42), metabolically unhealthy obesity with one component (HR 1.71; 95% CI, 1.12-2.61), and metabolically unhealthy obesity with ≥2 metabolic syndrome components (HR 2.77; 95% CI, 2.01-3.82) were associated with an increased risk of consecutive proteinuria. CONCLUSIONS: Metabolically healthy obesity did not increase the risk of consecutive proteinuria in Japanese middle-aged men.

Blood pressure components and the risk for proteinuria in Japanese men: The Kansai Healthcare Study.

BACKGROUND: We examined prospectively which of the four blood pressure (BP) components (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean arterial pressure [MAP]) was best in predicting the risk of proteinuria. METHODS: This prospective study included 9341 non-diabetic Japanese middle-aged men who had no proteinuria and an estimated glomerular filtration rate ≥60 mL/min/1.73 m2 and were not taking antihypertensive medications at entry. Persistent proteinuria was defined if proteinuria was detected two or more times consecutively and persistently at the annual examination until the end of follow-up. We calculated the difference in values of Akaike's information criterion (ΔAIC) in comparison of the BP components-added model to the model without them in a Cox proportional hazards model. RESULTS: During the 84,587 person-years follow-up period, we confirmed 151 cases of persistent proteinuria. In multiple-adjusted models that included a single BP component, the hazard ratios for persistent proteinuria for the highest quartile of SBP, PP, and MAP were 3.11 (95% confidence interval [CI], 1.79-5.39), 1.87 (95% CI, 1.18-2.94), and 2.21 (95% CI, 1.33-3.69) compared with the lowest quartile of SBP, PP, and MAP, respectively. The hazard ratio for the highest quartile of DBP was 2.69 (95% CI, 1.65-4.38) compared with the second quartile of DBP. Of all models that included a single BP component, those that included SBP alone or DBP alone had the highest values of ΔAIC (14.0 and 13.1, respectively) in predicting the risk of persistent proteinuria. CONCLUSIONS: Of all BP components, SBP and DBP were best in predicting the risk of persistent proteinuria in middle-aged Japanese men.

Relationship Between Alcohol Drinking Pattern and Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Moderate alcohol consumption has been reported to be associated with a decreased risk of cardiometabolic diseases. Whether drinking pattern is associated with the risk of proteinuria is unknown. METHODS: Study subjects were 9154 non-diabetic Japanese men aged 40-55 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73 m(2), no proteinuria, and no use of antihypertensive medications at entry. Data on alcohol consumption were obtained by questionnaire. We defined "consecutive proteinuria" as proteinuria detected twice consecutively as 1+ or higher on urine dipstick at annual examinations. RESULTS: During the 81 147 person-years follow-up period, 385 subjects developed consecutive proteinuria. For subjects who reported drinking 4-7 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was significantly associated with a decreased risk of consecutive proteinuria (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.36-0.80) compared with non-drinkers. However, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with an increased risk of consecutive proteinuria (HR 1.78; 95% CI, 1.01-3.14). For subjects who reported drinking 1-3 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was associated with a decreased risk of consecutive proteinuria (HR 0.76; 95% CI, 0.51-1.12), and alcohol consumption of ≥69.1 g ethanol/drinking day was associated with an increased risk of consecutive proteinuria (HR 1.58; 95% CI, 0.72-3.46), but these associations did not reach statistical significance. CONCLUSIONS: Men with frequent alcohol consumption of 0.1-23.0 g ethanol/drinking day had the lowest risk of consecutive proteinuria, while those with frequent alcohol consumption of ≥69.1 g ethanol/drinking day had an increased risk of consecutive proteinuria.

Drinking pattern and risk of chronic kidney disease: the kansai healthcare study.

BACKGROUND/AIMS: The association between alcohol consumption and the risk of chronic kidney disease (CKD) has been reported. What is not known is whether drinking pattern combined with the weekly frequency of alcohol consumption and the quantity per drinking day is associated with the risk of CKD. METHODS: We enrolled 9,112 Japanese nondiabetic men aged 40 to 55 years with absence of proteinuria, an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m(2) or higher, and not on antihypertensive medications at baseline. CKD was defined if eGFR was <60 ml/min/1.73 m(2). The weekly frequency classification was nondrinkers, 1-3 drinking days/week, or 4-7 drinking days/week. The quantity consumed per drinking day was classified as 0.1-23.0 g ethanol/drinking day, 23.1-46.0 g ethanol/drinking day, 46.1-69.0 g ethanol/drinking day, and ≥69.1 g ethanol/drinking day. RESULTS: During the 79,099 person-years, 1,253 subjects developed CKD. Compared to nondrinkers, those who consumed 23.1-46.0 or 46.1-69.0 g ethanol/drinking day on 4-7 drinking days/week had a decreased risk of CKD (multiple-adjusted hazard ratio (HR) 0.62 (0.52-0.74) and 0.76 (0.59-0.97), respectively). The association between the quantity per drinking day and the incidence of CKD was U-shaped among each category of the weekly frequency. HRs within similar categories of quantity per drinking day were lower in the 4-7 drinking days/week group than in the 1-3 drinking days/week group. CONCLUSION: Among middle-aged Japanese men, the people who drank middle-range quantity, specifically who drank 4-7 days/week, had lower risk of CKD than nondrinkers.

Sleep duration and the risk of future lipid profile abnormalities in middle-aged men: the Kansai Healthcare Study.

BACKGROUND: Although short sleep duration has been reported to be associated with future cardiometabolic diseases, it is not fully understood whether sleep duration is prospectively associated with the risk of each lipid profile abnormality. METHODS: Subjects were nondiabetic Japanese, 40-55 years of age, who were not taking oral lipid-lowering medications: for the incidence of low high-density lipoprotein cholesterol (HDL-C), 7627 men with an HDL-C level ≥ 40 mg/dL; for high triglycerides, 6973 men with a triglyceride level <200 mg/dL; for high low-density lipoprotein cholesterol (LDL-C), 7273 men with an LDL-C level <160 mg/dL; for high non-HDL-C, 7415 men with a non-HDL-C level <190 mg/dL; and for high total cholesterol (TC), 7196 men with a TC level <240 mg/dL. Lipid profile abnormalities were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program. RESULTS: During the 6-year observation period, there were 1022 cases of low HDL-C. Multiple-adjusted hazard ratios for low HDL-C were 0.79 (95% confidence interval, 0.64-0.97) for sleep durations of 5 to <7 h and 0.62 (0.46-0.83) for ≥ 7 h compared with <5 h. There were 1473 cases of high triglycerides. Multiple-adjusted hazard ratios for high triglycerides were 0.81 (0.68-0.98) for sleep durations of 5 to <7 h and 0.90 (0.72-1.13) for ≥ 7 h compared with <5 h. However, no association between sleep duration and the risk of future high LDL-C, non-HDL-C, or TC was observed. CONCLUSIONS: Moderate and/or long sleep durations decreased the risk of future low HDL-C and high triglycerides.

Serum butyrylcholinesterase and the risk of future type 2 diabetes: the Kansai Healthcare Study.

OBJECTIVE: Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes. DESIGN: A prospective cohort study. PARTICIPANTS: A total of 8470 Japanese men aged 40-55 years without type 2 diabetes at baseline. MEASUREMENTS: Type 2 diabetes was diagnosed if a fasting plasma glucose (FPG) level was ≥7·0 mmol/l, if a HbA1 c level was ≥6·5% or if participants were taking oral hypoglycaemic medication or insulin. RESULTS: During the 42,227 person-years of follow-up, 868 cases had developed type 2 diabetes. Serum butyrylcholinesterase was significantly positively correlated with body mass index (BMI), FPG, alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and triglycerides (TG), whereas negatively with high-density lipoprotein (HDL) cholesterol. In Cox proportional hazards models, after adjusting for age, BMI, FPG, alcohol consumption, smoking habit, walk to work, regular leisure-time physical activity and family history of diabetes, the highest quartile (398-806 IU/l) of serum butyrylcholinesterase increased the risk of type 2 diabetes compared with the lowest quartile (56-311 IU/l) [hazard ratio (HR) 1·41 (95% confidence interval (CI), 1·14-1·74)]. After further adjusting for ALT and GGT, this association remained [HR 1·40 (95% CI, 1·13-1·73)]. Furthermore, this association was significant independent of TG and HDL cholesterol. CONCLUSIONS: Elevated serum butyrylcholinesterase was independently associated with an increased risk of future type 2 diabetes.