Potential link between high FIB-4 score and chronic kidney disease in metabolically healthy men.

Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or proteinuria) and a habit of alcohol consumption were excluded. The cut-off FIB-4 score was 1.30, indicating increased risk of liver fibrosis. Overall, 5353 participants (men only) were analyzed without exclusion criteria. After propensity score matching, high FIB-4 score (≥ 1.30) was not an independent risk factor for incident CKD (odds ratio [OR] 1.57; 95% confidence interval [CI] 0.97-2.56). However, high FIB-4 score was a significant risk factor for CKD in non-obese (OR 1.92; 95% CI 1.09-3.40), non-hypertensive (OR 2.15; 95% CI 1.16-3.95), or non-smoking (OR 1.88; 95% CI 1.09-3.23) participants. In these participants, FIB-4 score was strongly associated with eGFR decline in the multiple linear regression analysis (ß = - 2.8950, P = 0.011). Therefore, a high FIB-4 score may be significantly associated with CKD incidence after 5 years in metabolically healthy participants.

Development of chronic kidney disease influenced by serum urate and body mass index based on young-to-middle-aged Japanese men: a propensity score-matched cohort study.

OBJECTIVE: To investigate the association between serum uric acid (SUA) level and body mass index (BMI) on the development of chronic kidney disease (CKD) in working men aged 20-60 years. DESIGN: Retrospective cohort study. SETTING: Data from employees' annual health check-ups were collected from two companies in 2009 and 2014. PARTICIPANTS: A total of 16 708 working men were recruited. We excluded participants with missing essential data (N=7801), who had basal estimated glomerular filtration rate (eGFR) <60.0 mL/min/1.73 m2 and/or proteinuria (N=698) or with the absence of follow-up data (N=2). PRIMARY OUTCOME: eGFR <60 mL/min/1.73 m2 and/or proteinuria (≥1+) in 2014 (defined as incident CKD). RESULTS: The cut-off values of SUA for incident CKD were 6.6 mg/dL in both young (20-39 years old) and middle-aged (40-60 years old) men analysed by receiver operator characteristics. ORs for incident CKD were assessed on propensity score-matched (1:1) cohorts. In young participants (N=1938), after propensity score matching, a coexistence of high-level SUA (≥6.6 mg/dL) and overweight (BMI ≥25 kg/m2) was a significant risk factor of incident CKD (OR=2.18, 95% CI 1.10 to 4.31, p=0.025), but high-level SUA was not an independent risk factor without overweight status (p=0.174). In middle-aged participants (N=2944) after propensity score matching, high-level SUA was a significant risk factor of incident CKD both with or without overweight (OR=1.44, 95% CI 1.02 to 2.04, p=0.037; OR=1.32, 95% CI 1.01 to 1.73, p=0.041, respectively). CONCLUSION: These findings suggest that high-level SUA is strongly associated with incident CKD in overweight young adult men.

Alteration of normal level of serum urate may contribute to decrease in estimated glomerular filtration rate decline in healthy Japanese men.

INTRODUCTION: Serum uric acid (SUA) levels have a linear relationship with the estimated glomerular filtration rate (eGFR). It is unclear whether further changes, subsequent to normal level of SUA can attenuate eGFR decline in a healthy population, so we aimed to determine the normal level of SUA that can contribute to preventing kidney dysfunction. METHODS: In this retrospective cohort study from Japan, annual health checkup data from 2009 to 2014 was collected. After propensity score matching (1:1), data from 2,634 individuals with basal SUA ≤7.0 mg/dL (normal; mean age, 39 y; mean eGFR, 80.8 mL/min/1.73 m2) and 1,642 individuals with basal SUA >7.0 mg/dL (elevated; mean age, 42 y; mean eGFR, 75.0 mL/min/1.73 m2) were collected to determine the relationship between followed-up SUA level and the rate of change in eGFR. RESULTS: In individuals with normal level SUA at baseline, the elevation of SUA (>7.0 mg/dL) accelerated eGFR decline compared to those with normal SUA levels at 5-year follow-up (-4.1 ± 9.6% vs -9.9 ± 9.0%, p < .0001). Digression of SUA level (≤7.0 mg/dL) reduced eGFR decline compared with persistent SUA level over 7.0 mg/dL (-1.5 ± 11.5% vs -7.0 ± 10.1, p < .0001). In multiple linear regression analysis, there was strong association between the rate of change in SUA and eGFR in individuals with basal SUA ≤7.0 and >7.0 mg/dL (standardized coefficient; -0.3348, p < .001 and -.2523, p < .001, respectively). CONCLUSION: Subsequent to normal level of SUA (under 7.0 mg/dL) may contribute to a decrease in eGFR decline in apparently healthy men.

Relationship between abdominal adiposity and incident chronic kidney disease in young- to middle-aged working men: a retrospective cohort study.

BACKGROUND: Obesity is a risk factor for the development of chronic kidney disease (CKD). However, it remains to be fully examined whether fatness is more useful in predicting incident CKD. We aimed this study to determine the association of body fat, body mass index and waist circumference (WC) with subsequent changes in estimated glomerular filtration rate (eGFR) and incident CKD in young- to middle-aged working men. METHODS: We analyzed data from annual health check-up in male workers aged from 20 to 60 years with basal eGFR of 60-90 mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident CKD were calculated by receiver operator characteristics analysis andχ2 test, respectively. We also tested trends of changes in eGFR according to changes in WC in each age decade. RESULTS: There were 8,015 men participants. During the 5-year follow-up, 11.0% of the participants (N = 878) had developed to incident CKD. When basal WC was greater than 80.0 cm, which was decided by Youden's Index, there was a significantly higher risk of incident CKD [OR 1.57 (95% confident interval 1.35-1.84)]. Changes in WC over 5 years were significantly related to eGFR decline in young men (< 40 years old) with normal blood pressures and normoglycemia. CONCLUSIONS: These findings suggest that WC > 80.0 cm is a risk factor for incident CKD and strongly associated with a decline in eGFR in the young- to middle-aged working healthy men.

Impact of low-density lipoprotein cholesterol on decline in estimated glomerular filtration rate in apparently healthy young to middle-aged working men.

BACKGROUND: It remains to be fully clarified whether there is a relationship between uncontrolled dyslipidemia and decline in estimated glomerular filtration rate (eGFR) in the general population. Therefore, this study's aim was to test the association of dyslipidemia with changes in eGFR in apparently healthy working men. METHODS: We retrospectively examined the annual medical check-up list of 14,510 male workers aged 20-60 years with eGFR ≥ 60 mL/min/1.73 m2 at baseline, and then evaluated the association of the changes in the check-up parameters with a decline in eGFR during the 5-year observation period. RESULTS: Mean age and eGFR were 38.5 years and 82.3 mL/min/1.73 m2 at baseline, respectively. Evaluated low-density lipoprotein cholesterol (LDL-C) (≥140 mg/dL) was a strong indicator of CKD development in participants (basal eGFR 60-90 mL/min/1.73 m2) without hypertension [odds ratio (95% confidence interval): 1.46 (1.12-1.90)] or diabetes mellitus (DM) [1.49 (1.23-1.82)]. When LDL-C normalized under 140 mg/dL during follow-up, the decline in eGFR was smaller in non-hypertensive participants [-5.9 (-14.4 to -0.9) vs -13.4 (-18.4 to -4.5) mL/min/1.73 m2, p < 0.05]. There was an inverse correlation between change of LDL-C and decline in eGFR (p for trend <0.001). CONCLUSION: Increased LDL-C levels are associated with the development of incident CKD and eGFR decline in young to middle-aged working men without hypertension and/or DM.

Distributions and ranges of values of blood and urinary biomarker of inflammation and oxidative stress in the workers engaged in office machine manufactures: evaluation of reference values.

BACKGROUND: Interleukins, interferons and oxidative DNA products are important biomarkers assessing the inflammations and tissue damages caused by toxic materials in the body. We tried to evaluate distributions, reference values and age related changes of blood levels of inflammatory cytokines, C-reactive protein (CRP), IgE and urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) among workers in a cohort study evaluating the health influences of toner particles. METHODS: A total of 1366 male workers under age 50 years (age 19-49 years; 718 exposed and 648 not exposed to toner particles) in a cross sectional study of 1614 (categorized as 809 exposed and 805 not exposed, age 19-59 years) workers in a photocopier company has been followed prospectively as the cohort. Blood levels of interleukin (IL)-4, IL-6, IL-8, interferon-γ (IFN-γ), CRP, IgE and urine 8-OHdG were measured annually for 5 years. RESULTS: Reference values of the biomarkers are; CRP: 0.01-0.63×10(-2) g/L, IgE: 6-1480 IU/mL, IL-4: 2.6-76.1 pg/mL, IL-6: 0.4-4.9 pg/mL and 8-OHdG: 1.5-8.2 ng/mgCr. We could not evaluate reference values for IL-8 and IFN- γ because most of the values were below the sensitivity limits (2.0 pg/mL and 0.1 IU/mL, respectively). There were no differences of the biomarker levels between the toner exposed and the control workers. We observed a statistically significant age related decrease of serum IL-4 levels. CONCLUSIONS: This is the first report assessing the distributions and reference values of inflammatory biomarker levels in a large scaled cohort. We observed age related changes of some of the biomarkers. We could not detect any differences of the studied biomarker values between the toner exposed and the control workers.

Cross-sectional study on respiratory effect of toner exposure.

In this baseline study, part of a cohort study to clarify the effect of toner exposure on the respiratory system, we surveyed 803 male toner workers and 802 referents with regard to their subjective respiratory symptoms and chest X-ray results. We also examined individual exposure history, current working conditions, and personal exposure levels to toner. There was a significantly higher prevalence of "coughing and sputum" related complaints among toner-exposed workers in the 30 and 40-year age groups. The group with toner-exposure history showed a higher odds ratio, by logistic regression, in relation to all questions regarding coughing. Mild fibrotic changes were observed in the chest X-rays of four workers who had engaged in toner-exposure work for at least a decade or more, and all four had reported allergic disease. Although we observed a tendency of higher prevalence of "coughing and sputum" in toner-exposed workers, the possibility of information bias cannot be eliminated. It should also be noted that this tendency did not exceed that of the general public. Further analysis is required in this ongoing 10-year cohort study to clarify the effect of toner exposure on the respiratory system.

Biological marker of furfural, chemicals without administrative control level.

Furfural, a colorless liquid used in solvent-extraction processes, petroleum refining and as a rubber additive, has been assigned an occupational exposure limit of 2.5 ppm by the Japan Society for Occupational Health, but an administrative control level for furfural has not been established. In order to conduct effective occupational health management in workplaces where furfural is used, we measured furfural concentrations in working environments and collected urine samples to measure furoic acid levels (one of the principal metabolites), which act as a biomarker of exposure to furfural. The measurements of airborne concentrations in a working environment where furfural or a solution containing furfural was handled were made in 2004. Workers answered a questionnaire on working conditions, urine samples were collected at the end of the workshift, and furoic acid in the urine was measured by gas chromatography/flame ionization detector (GC/FID). The ambient concentrations of furfural during the period were 2.1 ppm in a mixer room and 1.6 ppm in a filling room. The mean concentrations of furoic acid in the workers' urine were 7.7 +/- 7.8 mg/g-creatinine in summer and winter, respectively (normal range: 3 - 60 mg/g-creatinine). The average exposure to furfural per month calculated by multiplying the concentration in the working environment by working hours for a month was 86.4 +/- 108.6 ppm hours/months (mean +/- standard deviation) (range; 0 - 336 ppm hours/month). The relationship between average exposure to furfural and furoic acid in the urine was analyzed by simple linear regression analysis and a positive correlation was found. These findings suggest that furoic acid in urine is useful for biological monitoring of exposure to furfural, and that the measurement of both furfural in the environment and furoic acid in the urine are beneficial in occupational health management of furfural.