Different association of cigarette smoking with GFR estimated from serum creatinine and that from serum cystatin C in the general population.

BACKGROUND: Previous studies have shown that GFR estimated from serum creatinine (eGFRcr) is higher in smokers although the implications remain unclear. We aimed to clarify the associations of smoking with eGFRcys (GFR estimated from serum cystatin C) and eGFRcr, cys (the surmised most precise GFR estimate based on serum creatinine and cystatin C) in a working population. METHODS: Cross-sectional observation in 1,587 male workers aged 25-64 years. For eGFRcr, JEQcr proposed by the Japanese Society of Nephrology (JSN) and jEPIcr by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) modified for Japanese, and for eGFRcys, JEQcys proposed by JSN and EPIcys by CKD-EPI were calculated together with eGFRcr,cys of JEQaver (the average of JEQcr and JEQcys) and jEPIcr,cys by CKD-EPI modified for Japanese. RESULTS: Mean JEQcys was 95.1 mL/min/1.73 m(2) in contrast to 80.9 in JEQcr, with this difference considerable. Serum cystatin C was higher in smokers and obese subjects while serum creatinine was lower in smokers and slender subjects. JEQcys and EPIcys were lower in smokers while JEQcr and jEPIcr were higher in smokers adjusting for body mass index (BMI). eGFRcr,cys (JEQaver and jEPIcr,cys) did not differ between the never smokers and current smokers. eGFRcr,cys predicted by the equations composed of eGFRcr, BMI, and smoking habits showed a good accordance with calculated eGFRcr,cys. CONCLUSIONS: Either eGFRcr, eGFRcys or both were not reliable indicators of renal function in workers who smoked. The possibly more precise estimate of eGFRcr,cys could be predicted by eGFRcr, BMI and smoking in such a generally healthy population.

Elevated Blood Pressure and Serum γ -Glutamyltransferase as Significant Characteristics of Smokers With Chronic Kidney Disease.

BACKGROUND: Smoking is a risk factor for chronic kidney disease (CKD). However, it is speculated that only a small subset of sensitive smokers develop CKD. OBJECTIVES: We aimed to reveal the characteristics of such smokers sensitive to the renal effects of smoking with respect to cardiovascular (CV) risk factors associated with smoking and/or CKD. PATIENTS AND METHODS: Renal functions and CVD risk factors were assessed in middle-aged male workers. The patients were comprised of 336 nonsmokers, 332 smokers currently smoking up to one pack per day, and 38 who smoked more than one pack per day. CKD was determined by estimated glomerular filtration rate (eGFR) from serum creatinine and urinary albumin to creatinine ratio (ACR). The independent and interactive effects of smoking and CKD on the CVD risk factors adjusted for age, body mass index, alcohol consumption, and physical activity were statistically analyzed. RESULTS: In comparison to nonsmokers, smokers had significantly higher waist circumference, white blood cells (WBC), serum triglycerides, γ-glutamyltransferase (GGT), and C-reactive protein (CRP) and lower serum high-density lipoprotein cholesterol and uric acid. On the other hand, blood pressure (BP) and WBC tended to be higher in those showing CKD than others. Serum GGT and fasting plasma glucose were significantly higher, and insulin resistance index of homeostatic model assessment (HOMA-IR) tended to be higher in those with CKD. Serum CRP was especially high in those with moderate to severe CKD. A significant interactive effect of smoking and CKD on BP and serum GGT levels was detected, i.e. BP and GGT were not different in the subjects among nonsmokers with and without CKD, but were conspicuously high among smokers with CKD. No significant interactive effect was found on either HOMA-IR or serum CRP. CONCLUSIONS: Smokers with a higher BP and/or serum GGT may be at a higher risk of developing CKD. The associations of BP and serum GGT with CKD in smokers are not entirely mediated by increased insulin resistance or chronic inflammation caused by smoking.

Distribution of and factors contributing to chronic kidney disease in a middle-aged working population.

OBJECTIVES: To clarify the distribution of chronic kidney disease (CKD) and the factors contributing to its development and progression in middle-aged Japanese workers/employees. METHODS: This was a retrospective study involving 3,964 men and 2,698 women aged 35-64 years in 2009 who had been followed-up until 2003. Data on proteinuria determined with a dipstick and glomerular filtration rate estimated from serum creatinine concentration (eGFR) were collected in the annual health check-ups. RESULTS: Proteinuria was detected in 2.9 and 1.1 % of the men and women, respectively, and total CKD was detected in 16.0 and 16.1 % of the men and women respectively. Moderate or severe CKD associated a high risk of cardiovascular diseases and end-stage kidney disease was found mostly in the male subjects [2.0 (men) vs. 0.6 % (women)]. High-risk CKD was found in 3.3 % of the men aged 55-64 years. A body mass index (BMI) of ≥30, hypertension, diabetes mellitus (DM), current smoking and some job types were independently related to the development of proteinuria, while age, BMI, hypertriglyceridemia, and job types were related to total CKD. The development of high-risk CKD was related to preceding mild CKD signs of reduced eGFR and proteinuria as well as to hypertension, DM, smoking, and job type. CONCLUSIONS: Chronic kidney disease was found in 16 % of middle-aged workers with an equal prevalence in both sexes, while high-risk CKD was found mostly in men, of whom 3.3 % were aged 55-64 years. Obesity, hypertension, DM, smoking and some job types were related to the development and progression of CKD.

Smoking and chronic kidney disease in healthy populations.

The objective of this review is to explore the link between smoking and the development of chronic kidney disease (CKD) in generally healthy populations without pre-existing renal dysfunction such as diabetic nephropathy. Twenty-eight epidemiological studies concerning the renal effects of smoking in the general population were collected from the MEDLINE database and were reviewed for indications of proteinuria and/or the decline of glomerular filtration rate (GFR), and evaluated on the level of evidence and the quality of the study. Sixteen of the 28 studies were cross-sectional in design. Most articles had some weakness in scope, such as the 6 articles which did not fully exclude DM patients from the subjects, the 4 that did not consider the effects of ex-smoking, and the 3 that focused on only a small number of subjects. From these cases, it is difficult to draw firm conclusions. However, proteinuria or microalbuminuria was persistently high in current smokers; as much as 5-8% or 8-15% respectively, which was up to 2 to 3-times the rate of lifelong non-smokers. On the other hand, only 5 studies broader in scope detected any decline of GFR in smokers, while 9 other studies suggested a higher GFR in smokers than in non-smokers. Two good quality studies showed an even a significantly lower risk of a decreased GFR in smokers. These paradoxical CKD markers in smokers, i.e., a higher appearance of proteinuria with a higher GFR, could be a focus for further studies to reveal the underlying reasons for smoking-induced CKD. Workplaces may be an excellent place to study this subject since the long-term changes in renal function of smokers can be observed by collecting data in the annual health check-ups mandated at places of employment.

The effects of continuing and discontinuing smoking on the development of chronic kidney disease (CKD) in the healthy middle-aged working population in Japan.

OBJECTIVES: The strength of the association between smoking and the development of chronic kidney disease (CKD) in the healthy middle-aged working age population has not been established. METHODS: This was a retrospective 6-year observational study involving 4,121 male and 2,877 female workers who were free of primary kidney disease, diabetes mellitus, severe hypertension, and the signs and symptoms of CKD. Proteinuria was detected by a dipstick method, and glomerular filtration rate (GFR) was estimated by the equation of the Japan Society of Nephrology. RESULTS: Sixty men (1.5 %) and 21 women (0.7 %) developed proteinuria over the 6 years of the study. Irrespective of sex, in comparison with non-smokers, those who continued smoking showed an odds ratio (OR) of 2.52 with a 95 % confidence interval (CI) of 1.50-4.25 for developing proteinuria while those who quit smoking showed an OR of 1.29 (95 % CI 0.48-3.42), following adjustment for confounders. Among the study population, 443 men (10.7 %) and 356 women (12.4 %) developed a GFR of <60 mL/min/1.73 m(2), corresponding to stage III CKD. Continuing smokers had a low OR (0.74, 95 % CI 0.60-0.90) for developing a low GFR, as well as a higher mean GFR than non-smokers. The reduction in GFR during the 6-year study period was not different between smokers and non-smokers, but it was larger in those who developed proteinuria than in those who did not, irrespective of smoking. CONCLUSIONS: Continuing smokers showed a twofold or more higher risk of developing proteinuria. Discontinuation of smoking substantially reduced the risk. A longer observational period may be required to detect the smoking-induced risk of developing stage III CKD in the middle-aged working population.

Elevated Serum Gamma-Glutamyltransferase (GGT) Activity and the Development of Chronic Kidney Disease (CKD) in Cigarette Smokers.

BACKGROUND: Elevated serum gamma-glutamyltransferase (GGT) is predictive of various cardiovascular (CV) risk factors including chronic kidney disease (CKD). Elevated serum GGT has been recognized in smokers who are likely to develop CKD, but no study has focused on serum GGT and CKD in smokers. OBJECTIVES: The aim of this study was to clarify the associations between cigarette consumption, elevation of serum GGT and the development of proteinuria and CKD. PATIENTS AND METHODS: A retrospective 6-year observational study was conducted on 2,603 male workers aged between 40 and 64 years. Incidences of proteinuria detected by dipstick and CKD defined by proteinuria and/or reduced estimated glomerular filtration rate (eGFR) measured in health check-ups were determined 6 years later for those who had been free of them at baseline. RESULTS: Higher means of serum GGT in smokers than in nonsmokers at baseline, and a higher incidence of elevated serum GGT in smokers than in nonsmokers during the 6-year period were recognized only for alcohol consumers. Incidences of proteinuria and moderate or severe CKD which has a high risk of future renal failure or CV disease were higher in the subjects with greater cigarette consumption or a higher serum GGT level. Multiple logistic regression analyses adjusting for major CV risk factors showed a significant interactive effect between smoking and elevated serum GGT on the development of proteinuria and an additive effect of smoking and serum GGT on the development of high-risk CKD. CONCLUSIONS: Elevation of serum GGT in smokers, to a large extent, depends on the associated alcohol consumption. Elevated GGT in smokers plays at least a partial role in the development of CKD, mainly proteinuria, and the underlying mechanisms remain to be elucidated.

Cigarette smoking, proteinuria, and renal function in middle-aged Japanese men from an occupational population.

OBJECTIVES: To clarify the renal effects of cigarette smoking in a middle-aged occupational population because the effects have previously been demonstrated mainly in community populations that included many elderly people who are thought to be vulnerable to such effects. METHODS: In 990 middle-aged men recruited from a chemical plant, proteinuria was measured by a dipstick method and the glomerular filtration rate was estimated (eGFR) using a formula proposed by the Japanese Society of Nephrology. RESULTS: Proteinuria was found in 4.6% of the current smokers and 1.5% of the never-smokers. It was found in 4.8% of the subjects having a Brinkman index (BI) of 400-599 and 6.3% of those having a BI of 600 or above. The odds ratio for proteinuria in them was 2.94 (CI: 1.01-8.55) and 3.61 (CI: 1.29-10.1), respectively, adjusting for possible confounders. The mean eGFR was higher in smokers than in nonsmokers throughout middle age up to 64 years. Normal but high eGFR was found in 6.7% of the current heavy smokers and subnormal eGFR in 5.7% of the largest cumulative cigarette consumers in contrast to 3.0% or less of the never-smokers. Proteinuria was found in 13.3% of the subjects showing subnormal eGFR, specifically in 16.7% of the smokers and 8.3% of the nonsmokers. CONCLUSIONS: Smoking causes proteinuria in working middle-aged men. Smokers tend to have a high eGFR, but those with subnormal eGFR showed proteinuria most frequently. Whether the high eGFR in smokers will eventually decrease and cause proteinuria remains an important focus for further studies.

Cardiovascular and muscle activity during chewing in whiplash-associated disorders (WAD).

OBJECTIVE: The present study aimed to elucidate possible physiological mechanisms behind impaired endurance during chewing as previously reported in WAD. We tested the hypothesis of a stronger autonomic reaction in WAD than in healthy subjects in response to dynamic loading of the jaw-neck motor system. DESIGN: Cardiovascular reactivity, muscle fatigue indicies of EMG, and perceptions of fatigue, exhaustion and pain were assessed during standardised chewing. Twenty-one WAD subjects and a gender/age matched control group participated. Baseline recordings were followed by two sessions of alternating unilateral chewing of a bolus of gum with each session followed by a rest period. RESULTS: More than half of the WAD subjects terminated the test prematurely due to exhaustion and pain. In line with our hypothesis the chewing evoked an increased autonomic response in WAD exhibited as a higher increase in heart rate as compared to controls. Furthermore, we saw consistently higher values of arterial blood pressure for WAD than for controls across all stages of the experiment. Masseter EMG did not indicate muscle fatigue nor were there group differences in amplitude and mean power frequency. Pain in the WAD group increased during the first session and remained increased, whereas no pain was reported for the controls. CONCLUSION: More intense response to chewing in WAD might indicate pronounced vulnerability to dynamic loading of the jaw-neck motor system with increased autonomic reactivity to the test. Premature termination and autonomic involvement without EMG signs of muscle fatigue may indicate central mechanisms behind insufficient endurance during chewing.

Association between cigarette consumption and proteinuria in healthy Japanese men and women from an occupational population.

The association between cigarette consumption and prevalence of mild proteinuria (30-99 mg/dl of albumin) was analyzed in 11,569 male and 4,715 female workers aged 18-67 yr recruited from an occupational population. Proteinuria was found in 274 (2.4%) of the total male workers and in 50 (1.1%) of the total females. Stepwise logistic regression analyses showed that sex, suspected diabetes mellitus, blood pressure (BP) and Brinkman Index (BI) levels (0, 1-199, 200-499, 500-799, 800-) were significantly related to proteinuria, and that the odds ratio of each BI level for proteinuria was 1.11 (C.I.: 1.01-1.67). In the subjects aged 50 yr or older, after excluding those suspected of having hypertension and/or diabetes mellitus, the odds ratio reached 1.37 (C.I.: 1.15-1.63), with the gender difference then no longer significant. The odds ratio for proteinuria was calculated as 5.44 (C.I.: 2.27-13.0) in male and female smokers having a BI of 500 or above and normal-high BP (130-139/85-89 mmHg) in comparison with nonsmokers having normal BP (<130/85 mmHg). These results suggest that heavy cigarette consumption represented by a BI of 500 or above is a risk factor of proteinuria even in healthy Japanese workers, particularly in those aged 50 yr or older and having normal-high BP.

Low fasting serum insulin in Japanese alcohol consumers does not imply improved coronary risk factors.

OBJECTIVE: The effects of alcohol consumption on coronary risk factors (CRFs) and insulin resistance (IR) have seemed equivocal in previous studies. This study aimed to clarify the implications of low fasting blood insulin observed in alcohol consumers as related to CRFs and IR. METHODS: A cross-sectional observation in 2133 middle-aged healthy Japanese men for associations of increases in alcohol consumption, fasting serum insulin concentration and serum gammaglutamyltransferase (GGT) activity with the major CRFs of high systolic blood pressure (SBP), fasting serum glucose, triglycerides (TG), total- and LDL-cholesterol (tCh&LDLc) and low serum HDL-cholesterol (HDLc). RESULTS: Increased alcohol consumption was related to higher SBP, serum GGT, glucose and HDLc, and lower serum LDLc and insulin. Although high serum insulin was significantly related to all of the CRFs in all nondrinkers, moderate drinkers consuming up to 59 ml of alcohol per day and excessive drinkers consuming more, the means of SBP, serum glucose and HDLc were significantly higher and serum LDLc was lower in drinkers than in nondrinkers at any level of serum insulin, indicating that the good and bad profiles of CRFs in alcohol consumers are independent of their low fasting serum insulin. High serum GGT related to increased alcohol consumption and/or body weight was significantly associated with high serum insulin and all of the CRFs in all categories of alcohol consumption. CONCLUSIONS: Low fasting serum insulin observed in drinkers does not imply improved CRFs, and thus may not imply improved IR. High serum GGT may reflect increased IR in both drinkers and nondrinkers.

Alcohol consumption, serum gamma-glutamyltransferase levels, and coronary risk factors in a middle-aged occupational population.

The relationships between alcohol consumption, serum gamma-glutamyltransferase (GGT) levels, and the prevalence of major coronary risk factors were analyzed cross-sectionally in 2,399 male and 1,402 female middle-aged workers, to clarify the effects of moderate alcohol consumption on the development of the metabolic syndrome. Male moderate drinkers, consuming less than 60 ml of alcohol per day, had a lower prevalence of upper body obesity and low serum HDL-cholesterolemia (LHDLC) in comparison with nondrinkers, but not of hypertension, impaired glucose tolerance or hypertriglyceridemia (HTG). In women, alcohol consumption did not show any significant associations with the coronary risk factors. Men with an elevated serum GGT (EGGT) of 40 U/l or above had a significantly higher odds ratio for all the coronary risk factors as compared with those with normal GGT, even after adjusting for alcohol consumption, together with age, body mass index, cigarette consumption and physical activity. Women with an EGGT of 25 U/l or above had similar findings, although significance was found only in HTG. Nearly 80% and 55% of the appearance of EGGT in men and women were attributable to alcohol consumption, and 20% and 10% of the male and female moderate drinkers had EGGT. These results suggest that even moderate alcohol consumption will increase coronary risk factors characteristic of the metabolic syndrome in drinkers who have an increase in serum GGT. Further studies are required to confirm the causal association between alcohol consumption, increase in serum GGT and development of the metabolic syndrome.

Urinary cadmium excretion is correlated with calcaneal bone mass in Japanese women living in an urban area.

Nine hundred eight women aged 40-88 years living in a non-Cd-polluted area in Japan were analyzed for urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG) activity, beta(2)-microglobulin (B2MG) concentration, and for the stiffness index (STIFF) of calcaneal bone using an ultrasound method. The urinary Cd in the subjects, with a mean and range of 2.87 and 0.25-11.4 microg/g creatinine, respectively, showed a significant correlation with NAG but not with B2MG. STIFF was significantly inversely correlated with urinary Cd, and the association remained significant after adjusting for age, body weight, and menstrual status, suggesting a significant effect of Cd on the bone loss in these subjects without signs of Cd-induced kidney damage. A two-fold increase in urinary Cd was accompanied by a decrease in STIFF corresponding to a 1.7-year rise in age. These results emphasize the need for reassessment of the significance of Cd exposure in the general Japanese population.

Impact of obesity on musculoskeletal pain and difficulty of daily movements in Japanese middle-aged women.

OBJECTIVE: To investigate the impact of obesity on musculoskeletal pain and disability, which impairs well-being, associations between body mass index (BMI), frequency of musculoskeletal pain and difficulty of daily movements were assessed in middle-aged women. METHODS: Subjects were 709 Japanese women in a community, aged 40-69. Measured BMI, current smoking habits, frequency of pain (pain score)(rarely (0), occasionally (1) or frequently (2)) during the last 1 month at shoulders, neck, upper back, lower back and legs, difficulty of three daily movements: walking continually for more than a half hour, climbing stairs and sitting on the floor with one's legs bent beneath one another, (score for each movement) (rarely (0), occasionally (1) or frequently (2)) by a questionnaire. The summed score was defined as the difficulty score of daily movements (DS) (0-6). RESULTS: BMI increased significantly with age. Lower back pain (occasionally or frequently) was the most common symptom (40.3%) in the subjects. There was a peak in prevalence of frequent pain of shoulders at age 50. Pain score for legs and DS increased significantly with age. Higher BMI was related to increased prevalence of frequent leg pain and DS (>or=3), but there were no significant associations between age or BMI, and scores of back pain. DS was correlated significantly with pain scores at shoulders, upper back, lower back and legs. After adjustment for age and smoking habit using a logistic regression analysis, odds ratios for frequent pain at legs and DS (>or=3) were 4.02 (CI: 1.83-8.80) and 2.92 (CI: 1.56-5.47), respectively, in the obese women (BMI>or=26.4, n=61), compared with 401 women with normal BMI (20-24). CONCLUSION: Obesity tended to impair well-being through musculoskeletal pain at legs and difficulty of daily movements in Japanese middle-aged women.