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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 m 2 ., 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.

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 m 2 , 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/m 2 . 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.

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 m 2 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., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

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.

Background and Objectives: Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far., Design, Setting, Participants, & Measurements: This study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR ≥117.0 ml/min per 1.73 m(2), which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick., Results: During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a dose-response manner., Conclusions: In middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.

Background/aims: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR)., Methods: We enrolled 10,008 Japanese men aged 40-55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m(2)., Results: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≥7.51 × 10(3)/μl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile (≤4.80 × 10(3)/μl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR., Conclusion: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR., (Copyright © 2011 S. Karger AG, Basel.)