Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey

Nephrology Dialysis Transplantation, Feb 2010

Background. The prevalence of chronic kidney disease (CKD) has been increasing throughout the world over the last decade. Metabolic syndrome (MS) has been known to be an independent risk factor of CKD. However, both renal and metabolic diseases are experienced differently in men and women, and clinical implication of MS on CKD may be different according to gender. Methods. To understand the association between MS and CKD, we performed a cross-sectional study in non-institutionalized civilians using the data of the Korean National Health and Nutrition Examination Survey. Of 37 769 participants, 5091 were available for the analysis of the prevalence of CKD (defined as dipstick proteinuria or a reduced GFR < 60 ml/min/1.73 m2). Results. The prevalence of CKD was 8.9% (7.4% in men, 4.7% in premenopausal women and 20.1% in postmenopausal women) and MS was seen in 26.2% (24.9% in men, 13.9% in premenopausal women and 52% in postmenopausal women). The prevalence of CKD increased with ageing, in particular after sharply after the age of 50 in both genders. MS was a significant determinant of CKD; however, sub-analysis revealed that MS was a risk factor for CKD only in men under the age of 60 and in postmenopausal women. Neither MS per se nor individual components of MS were associated with CKD in men over the age of 60 and in premenopausal women. Conclusion. Differential effect of MS on CKD according to age and gender in our study may provide a clue to define the subject in need for more attention for the treatment of MS in terms of the development of CKD.

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Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey

NHANES III). Am J Kidney Dis Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey Mina Yu 0 Dong-Ryeol Ryu 0 Seung-Jung Kim 0 Kyu-Bok Choi 0 Duk-Hee Kang 0 0 Division of Nephrology, Department of Internal Medicine, School of Medicine, Ewha Medical Research Center, Ewha Womans University , Seoul , Korea Background. The prevalence of chronic kidney disease (CKD) has been increasing throughout the world over the last decade. Metabolic syndrome (MS) has been known to be an independent risk factor of CKD. However, both renal and metabolic diseases are experienced differently in men and women, and clinical implication of MS on CKD may be different according to gender. Methods. To understand the association between MS and CKD, we performed a cross-sectional study in noninstitutionalized civilians using the data of the Korean National Health and Nutrition Examination Survey. Of 37 769 participants, 5091 were available for the analysis of the prevalence of CKD (defined as dipstick proteinuria or a reduced GFR < 60 ml/min/1.73 m2). Results. The prevalence of CKD was 8.9% (7.4% in men, 4.7% in premenopausal women and 20.1% in postmenopausal women) and MS was seen in 26.2% (24.9% in men, 13.9% in premenopausal women and 52% in postmenopausal women). The prevalence of CKD increased with ageing, in particular after sharply after the age of C The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: chronic kidney disease; gender difference; metabolic syndrome - Received for publication: 13.5.09; Accepted in revised form: 17.8.09 50 in both genders. MS was a significant determinant of CKD; however, sub-analysis revealed that MS was a risk factor for CKD only in men under the age of 60 and in postmenopausal women. Neither MS per se nor individual components of MS were associated with CKD in men over the age of 60 and in premenopausal women. Conclusion. Differential effect of MS on CKD according to age and gender in our study may provide a clue to define the subject in need for more attention for the treatment of MS in terms of the development of CKD. Introduction The number of chronic kidney disease (CKD) patients has been increasing throughout the world over the last decade and is expected to continue growing [1,2]. A rise in the incidence of CKD in recent years paralleled with an increasing prevalence of metabolic syndrome (MS) [3–5]. Several papers based on epidemiologic investigation from different countries revealed that MS per se is an independent risk factor of CKD with a graded relationship between individual traits of MS and the prevalence of CKD [6–8]. Since both renal and metabolic disease are experienced differently in men and women, clinical implication of MS on CKD may be different according to gender [9,10]. However, no studies addressed the gender-specific role of MS in the development of CKD. To investigate whether the clinical significance of MS as a cause of CKD is dependent on age, gender or menopausal status, we performed a crosssectional study using data from a large, community-based cohort in Korea. Subjects and methods Study population We used data from the Korean National Health and Nutrition Examination Survey (NHANES) in 2001. The Korea NHANES is a national survey conducted in non-institutionalized Korean civilians, which employed a multi-stage probability sampling method based on the 2000 Korean National Census Registry. A total of 37 769 subjects participated in the 2001 Korea NHANES. Of these, 5091 subjects aged from 20 to 79 years (2139 men and 2952 women) with available information of renal function and all parameters related to lifestyle were included to assess the prevalence of MS and CKD. All participants completed a health interview survey that included the information regarding medication, smoking, alcohol consumption, physical activity and menopausal status. Smoking status was defined as nonsmokers, current smokers and ex-smokers. Alcohol consumption was categorized according to the amount and frequency of alcohol consumed: none, current drinker, risk drinker and high-risk drinker [11]. Menopause was defined as amenorrhoea for 12 months following the final menstrual period. Health examination: anthropometry, blood pressure and biochemical parameters A health examination survey included anthropometric measurement, blood pressure measurement and blood chemistry test. Blood pressure was measured twice with a standard mercury sphygmomanometer (Baumanometer R W. A. Baum Co., New York, USA) while seated after a 10-min rest. Blood samples were collected in the morning after an overnight fast, then centrifuged and transferred to a national central laboratory. Total cholesterol, triglyceride, HDL cholesterol and fasting plasma glucose were measured using an autoanalyser (Hitachi-747, Tokyo, Japan). LDL cholesterol level was calculated using the Friedewald equation [12]. Serum creatinine was measured by the modified Jaffe kinetic reaction in a national central laboratory. To calculate eGFR by Modification of Diet in Renal Disease (MDRD) equation [13], we indirectly calibrated the measured creatinine level for variance with those of the MDRD clinical laboratories. The serum creatinine level was also adjusted by a two-step process as previously published [14,15]. Definition of MS and CKD MS was defined using the criteria recommended in the National Cholesterol Education Program Adult Treatment Panel III (NCEP) guidelines with modification of waist circumference [16,17]. Specifically, elevated blood pressure was defined as both measurement of systolic and diastolic blood pressure of ≥135/85 mmHg and current use of antihypertensive medication. Elevated blood glucose was defined as a fasting blood glucose of 110 mg/dl or greater or use of glucose-lowering medicine. The low HDL cholesterol was defined as <40 mg/dl in men and <50 mg/dl in women. Hypertriglyceridaemia was defined as a serum triglyceride of 150 mg/dl or greater. Abdominal obesity was defined as a waist circumference >90 cm in men and >80 cm in women according to the Asia-Pacific criteria. MS was defined as the presence of three or more of these five components. CKD was defined as a GFR of <60 ml/min/1.73 m2 or proteinuria by a dipstick urine analysis score of 1+ or more [18]. The diagnosis of diabetes was based on three criteria of the revised American Diabetes Association (ADA) recommendation [19] or current history of taking a glucose-lowering medicine. Data were presented as mean, standard deviation for continuous variables and as percentage for categorical variables. The presence of MS and its traits were compared between subjects with CKD and those without CKD by Student’s t-test for continuous variables and by the chi-square test for categorical variables. Logistic regression analysis was used to determine the crude and age, gender, the presence of diabetes and body mass index (BMI) adjusted odds ratios (OR, 95% CI) of CKD according to the presence of MS or each trait of MS. We calculated the P-value for trend in the prevalence of CKD according to the number of MS and ages using logistic regression analysis. To evaluate the gender and age difference in the relationship between MS and CKD, we stratified participants by gender, age and menopausal status. With these subgroups, we calculated the crude and adjusted odds ratio of CKD according to the presence of MS, traits of MS and the number of traits of MS. In the multivariate model, we adjusted the risk for potential confounding factors: age, the presence of diabetes, physical inactivity, cigarette smoking, alcohol drinking and menopause. All statistical analyses were performed by using the SPSS software (SPSS Version 13, SPSS Inc, Chicago, IL, USA). A P-value < 0.05 was considered statistically significant. Results Demographic characteristics of subjects and the prevalence of MS The demographic characteristics of 5091 subjects are summarized in Table 1. The prevalence of MS was 26.2% (24.9% in men and 27.1% in women) by the criteria of NCEP-ATP III with the Asia-Pacific Modification of waist circumference, while it was 18% by the NCEP-ATP III criteria. Among five risk factors of MS, low HDL concentration (49%) was most common, followed by high blood pressure (34%), central obesity (33.6%), high triglyceride (33.1%) and high fasting glucose (16.2%). Characteristically, mean HDL cholesterol was 46.5 mg/dl which was lower compared to the values of the USA or Japan [6,7]. The prevalence of each component of MS in men and women is shown in Table 2, which reveals a higher prevalence in high blood pressure and hypertriglyceridaemia in men and low HDL cholesterol and central obesity in women. Characteristics of subjects with CKD The mean eGFR of the subjects was 78.9 ml/min/1.73 m2 with a prevalence of CKD of 8.9%. Subjects with CKD were older and obese with higher BMI compared to those without CKD (Table 3). The prevalence of individual components of MS as well as MS per se was higher in subjects with CKD (Table 3). There was no significant difference in the status of smoking, alcohol consumption or physical inactivity in subjects with or without CKD (Table 3). Prevalence of CKD and MS according to age and gender The prevalence of CKD was increased with age in both men and women with a sharp increase after the age of 50, particularly in women (Figure 1). Nearly 25.9% of the Data are expressed as mean (SD) (minimum–maximum) or number (%). BP, blood pressure; eGFR, estimated GFR; CKD, chronic kidney disease. 533 (24.9) 891 (41.7) 340 (15.9) 851 (39.8) 929 (43.4) 489 (22.9) 800 (27.1) 839 (28.4) 408 (13.8) 1859 (63) 761 (25.8) 1213 (41.1) Metabolic syndrome (%)a High blood pressure (%)b High glucose (%)c Low HDL (%)d High triglyceride (%)e Central obesity (%)f aMetabolic syndrome was defined as the presence of three or more of the risk factors. bSystolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg or taking antihypertensive medication. cFasting glucose level ≥110 mg/dl or use of insulin or hypoglycaemic medication. dHDL cholesterol <40 mg/dl in men or < 50 mg/dl in women. eSerum triglyceride ≥150 mg/dl. f Waist circumference >90 cm in men or >80 cm in women. participants aged 60 years and older had CKD. The prevalence of MS in men showed a gradual increase with age and reached a peak at the age of 60. However, in women, the prevalence increased sharply with age, especially after 40 years of age. MS was more prevalent in men than women under 50 years of age, but the prevalence was reversed after the age of 50 (Figure 1). Interestingly, an increase in the prevalence of CKD was preceded by an increase in MS in both genders. Values are expressed as mean (SD). CKD (+) (n = 455) CKD (−) (n = 4636) Sub-analysis of an individual risk factor of MS according to age and gender revealed that high blood pressure was responsible for a sharp increase in the prevalence of MS in women after the age of 50 (Figure 2) since the presence of other components of MS other than high blood pressure was comparable in each age group of subject with MS. Impact of MS and its components on the prevalence of CKD The clinical characteristics of the subjects by the presence of MS are summarized in Table 4. The mean concentrations of blood urea nitrogen (BUN) and creatinine were higher in subjects with MS associated with a lower eGFR compared to their counterpart. The mean prevalence of CKD was significantly higher in the MS group than in the subjects without MS (16.6 versus 6.2%, P < 0.001). Figure 3 shows a higher prevalence of CKD in subjects with MS in each age group. However, when we analysed the data in subgroup of participants divided by age and gender, MS showed a differential association with CKD according to age and gender. In men, the prevalence of CKD was higher in subjects with MS in all age groups but with a significant difference in men under the age of 60 (Figure 3), whereas it became significantly higher only after the age of 50 in women with MS compared to women without MS. Table 5 shows the detail of the prevalence of CKD according to age, menopausal status and the presence of MS in men and women. The prevalence of CKD in men was 13.5% and in the subjects with or without MS it was 5.4% (P < 0.001); however, the difference in the prevalence of CKD according to the presence of MS was only observed in men <60 years (Table 5). Similarly, a statistical difference in the prevalence of CKD in women in the presence of MS was only seen in postmenopausal women (Table 5). Taken together, as seen in Figure 4, the difference in the prevalence of CKD in the presence of MS was statistically significant only in younger men and postmenopausal women. P-value Age (years) 52.8 (14.0) 41.3 (13.8) <0.001 Body weight (kg) 66.6 (11.3) 60.0 (9.8) <0.001 Height (cm) 160.0 (9.6) 162.6 (8.6) <0.001 BMI (kg/m2) 25.9 (3.1) 22.6 (2.8) <0.001 Waist circumference (cm) 89.5 (7.5) 77.8 (8.4) <0.001 Mean systolic BP (mmHg) 136.1 (19.1) 117.4 (16.0) <0.001 Mean diastolic BP (mmHg) 84.3 (11.2) 74.7 (10.5) <0.001 Fasting glucose (mg/dl) 107.2 (22.7) 93.6 (13.1) <0.001 HDL cholesterol (mg/dl) 40.6 (8.6) 48.6 (10.2) <0.001 Triglyceride (mg/dl) 198.6 (82.0) 115.4 (63.7) <0.001 BUN (mg/dl) 14.2 (3.9) 13.6 (3.8) <0.001 Creatinine (mg/dl) 0.976 (0.174) 0.960 (0.168) <0.001 eGFR (ml/min/1.73 m2) 74.5 (13.1) 80.5 (12.9) <0.001 Chronic kidney disease (%) 221 (16.6) 234 (6.2) <0.001 eGFR<60 ml/min/1.73 m2 (%) 182 (13.7) 177 (4.7) <0.001 Proteinuria (%) 53 (4.0) 66 (1.8) <0.001 Diabetes (%) 262 (19.7) 79 (2.1) <0.001 Smoking (%) 476 (35.7) 1373 (36.5) 0.590 Alcoholc consumption (%) 188 (14.1) 516 (13.7) 0.735 Physical inactivity (%) 977 (73.5) 2683 (71.4) 0.166 Data expressed as mean (SD) or number (%). Not only MS per se, but the number of risk factors of MS was also related to the presence of CKD. There was a significant graded relationship between the number of components present and the corresponding prevalence of CKD (P < 0.05). Relative risk of CKD according to the presence of MS Table 6 shows crude and multivariate-adjusted odds ratio of CKD, indicating that MS per se is a risk factor of CKD. Interestingly, not all the components of MS appeared to be associated with CKD after an adjustment for age, gender, BMI and the presence of diabetes. Hypertriglyceridaemia, high blood pressure and high fasting glucose were associated with an increased odds ratio of CKD in our subject. Similar to the association between MS and CKD, the presence of each trait of MS was a significant risk factor for CKD in men under the age of 60 years. However, MS per se or its components, with the exception of high blood pressure, was not associated with an increased odds ratio of CKD in men over the age of 60 years (Table 7). In women, multiple regression analysis revealed MS per se as a risk factor for CKD, only in postmenopausal women. In premenopausal women, neither MS per se nor individual components of MS had increased odds for CKD. Value within ( ) is the percentage in each group. CKD, chronic kidney disease; MS, metabolic syndrome. Men (n = 2139) 72/533 (13.5) 40/390 (10.3) 32/143 (22.4) 86/1606 (5.4) 41/1367 (3.0) 45/239 (18.8) Table 8 and Figure 5 show the odds ratio of the numbers of the risk factors of MS to CKD in men and women. There was a statistically significant trend between the number of risk factors and the prevalence of CKD; however, it was statistically significant only in men <60 years of age and in postmenopausal women. Discussion MS and CKD are two representative diseases showing the most noticeable worldwide epidemic in modern society [20,21]. MS is known to be associated with an increased risk of CKD in cross-sectional [6–8] and longitudinal studies [22–27]. The prevalence of MS in this study was 26.2% by the criteria of NCEP with Asia-Pacific modification of abdominal obesity, while it was 18.2% by NCEP-ATP-III, which is lower than that in the USA (24.7%) and higher than in Japan (12.4%) [6,7,28]. Previous reports showed that subjects with MS had a 1.86–2.08 times greater risk of CKD than subjects without MS even after adjustment for multiple risk factors of renal disease progression [6,23]. The results of our study conducted in a non-institutional general population is consistent with previous results, demonstrating a 1.43 times greater risk of CKD in subjects with MS after an adjustment for age, gender, BMI, physical inactivity and smoking. Since diabetes is an unquestionable risk factor for CKD, we also adjusted Women (n = 2952) 149/800 (18.6) 16/268 (6.0) 133/532 (25) 148/2152 (6.9) 75/1661 (4.5) 73/491 (14.9) the risk of CKD for the presence of diabetes and found that the odds ratio of MS for CKD was 1.45 (P = 0.03), suggesting MS per se was a risk factor of CKD independent of diabetes. Although the association of CKD with MS was independent of age and gender in this study, there were several differences in clinical significance of MS and its individual traits on CKD in men and women. The first interesting finding of our study was a prominent increase in the prevalence of both MS and CKD in women after the age of 50. It is well known that the prevalence of cardiovascular and renal disease increases with age in both men and women [3]; however, there have been few studies comparing the prevalence of MS and CKD in men and women with ageing. One Japanese cohort with a similar distribution of age and gender and the same criteria of MS and CKD as our study showed a different result in age- and genderrelated prevalence of both diseases from our study [7]. They showed a higher prevalence of MS and CKD in men in all age groups from 30 to 79 years. However, a Chinese study in 15 540 adults aged 36–74 years showed a significantly higher prevalence of MS in women (17.8% versus 9.8%, women versus men, P < 0.001) associated with a higher prevalence of obesity (31.1% versus 26.9%) in women than men [29]. The prevalence of MS is reported to be comparable in men and women in the USA and Europe [6,30,31]. Therefore, it is assumed that there is a difference in the gender-related prevalence of MS in different countries or Metabolic syndrome Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted Central obesity Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted Low HDL cholesterol Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted High triglyceride Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted High blood pressure Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted High fasting glucose Crude Age adjusted Age, gender adjusted Age, gender, BMI adjusted Age, gender, BMI, diabetes adjusted OR (95% CI) 2.993 (2.461, 3.640) 1.664 (1.348, 2.054) 1.616 (1.306, 1.999) 1.433 (1.131, 1.815) 1.448 (1.136, 1.846) 2.219 (1.828, 2.694) 1.433 (1.167, 1.759) 1.333 (1.076, 1.653) 1.022 (0.773, 1.351) 1.020 (0.771, 1.349) 1.423 (1.169, 1.733) 1.167 (0.949, 1.434) 1.075 (0.867, 1.331) 1.020 (0.822, 1.266) 1.019 (0.821, 1.265) 1.792 (1.475, 2.177) 1.390 (1.134, 1.704) 1.463 (1.190, 1.798) 1.351 (1.090, 1.670) 1.350 (1.092, 1.668) 3.240 (2.659, 3.947) 1.542 (1.236, 1.924) 1.600 (1.279, 2.003) 1.479 (1.176, 1.859) 1.478 (1.175, 1.859) 2.316 (1.851, 2.899) 1.472 (1.161, 1.867) 1.479 (1.165, 1.878) 1.358 (1.065, 1.733) 1.584 (1.167, 2.149) CKD, chronic kidney disease; BMI, body mass index; HDL, high-density lipoprotein. different ethnic groups despite considering the use of different criteria of MS. Analysis revealed that a steep increase in MS in women in our study was attributable to an increase in the prevalence of high blood pressure in women with ageing (Figure 2). The NCEP definition gives equal weight to each MS trait; however, the prevalence and the impact of each trait may vary in different ehnic groups [16,32]. Kitiyakara et al. showed that high blood pressure was associated with an increased risk of the prevalence of CKD, whereas elevated fasting blood sugar was a determinant of new CKD in their cross-sectional and prospective study in the Southeast Asian population [33]. In our study, although low HDL cholesterol was not a significant determinant of CKD after an adjustment for age, gender and BMI, the prevalence of low HDL cholesterol was characteristically higher, especially in women compared to the results of other studies from North America and Asia [6,7]. The reasons for this high prevalence of low HDL cholesterol especially in among women remain unclear. Koreans consume relatively little fat compared with the Westerners because their meals are carbohydrate dominant. Relatively low-fat diet and an uncertain genetic factor may explain why Koreans have low HDL cholesterol level [34,35]. One of the most interesting findings of this study is the differential association between MS and CKD in men and women according to their age and menopausal status. Although MS was a significant risk factor for CKD both in men (OR 2.373, P = 0.014) and women (OR 1.432, P = 0.014) even after the adjustment for age, diabetes, physical inactivity, smoking and alcohol consumption, the association was significant only in men under the age of 60 and postmenopausal women. All traits of MS were associated with a significant odds ratio of CKD in men under the age of 60 years, but only high blood pressure was a significant predictor of CKD in men over the age of 60. Tanaka et al. also reported in their cross-sectional study a significance of MS as a determinant of CKD only in younger men (<60 years) [7]. This finding suggests that the MS may be not a key determinant of CKD in older men who already have other risk factors of CKD such as age-dependent atherosclerosis. In women, the presence of MS was not a significant determinant of CKD in premenopausal women (OR 1.343, 0.770–2.341, P = 0.30); however, MS per se as well as high triglyceridaemia and high blood pressure was associated with a significant risk for CKD in postmenopausal women. Although it is controversial whether Metabolic syndrome Central obesity Low HDL cholesterol High triglyceride High fasting glucose Two componentsa Three componentsa Four componentsa Five componentsa BMI, body mass index; BP, blood pressure; HDL, high-density lipoprotein. aCrude OR. bAdjusted for age, diabetes, physical inactivity, smoking and alcohol consumption. cAdjusted for age, diabetes, physical inactivity, smoking, alcohol consumption and menopause. OR (95% CI) 3.701 (2.351, 5.805) 1.243 (0.752, 2.073) 2.373 (1.627, 3.370) 2.256 (1.550, 3.894) 1.252 (0.726, 2.160) 1.836 (1.277, 2.640) 1.575 (1.008, 2.462) 1.277 (0.774, 2.107) 1.361 (1.112, 1.915) 2.601 (1.629, 4.153) 1.277 (0.774, 2.107) 2.103 (1.488, 2.971) 2.585 (1.644, 4.064) 1.853 (1.029, 3.336) 2.500 (1.729, 3.614) 3.309 (2.041, 5.365) 1.676 (0.969, 2.898) 2.172 (1.504, 3.137) OR (95% CI) 2.388 (1.279, 4.459) 2.347 (1.205, 4.573) 2.403 (1.517, 3.807) 3.840 (2.033, 7.254) 1.367 (0.656, 2.886) 2.434 (1.487, 3.988) 9.038 (4.420, 18.484) 3.353 (1.419, 7.925) 6.081 (3.406, 10.856) 12.533 (3.802, 41.317) 2.980 (0.826, 10.755) 7.033 (2.748, 17.997) aCompared to those with 0 and 1 component of metabolic syndrome in each gender. bCrude OR. cAdjusted for age, diabetes, physical inactivity, smoking and alcohol consumption. dAdjusted for age, diabetes, physical inactivity, smoking, alcohol consumption and menopause. menopause increases the risk of the disease independent of normal ageing, many studies have revealed that menopause per se is an independent risk factor of cardiovascular and other diseases. Postmenopausal status is also known to be associated with a 60% increased risk of MS [36], even after adjusting for compounding variables, such as age, body mass index and physical activity. There has been no study investigating whether menopause per se can be a risk factor for CKD or not. In our study, menopause was an independent risk factor of MS and CKD even after the adjustment with age, gender and BMI. The reason for the differential effect of MS on the presence of CKD is not clear. This age- and menopausal statusdependent association of MS with CKD in men and women raised the possibility of hormonal status as a determinant of clinical significance of MS. In our study, MS was a significant determinant of the presence of CKD only in subjects with androgenic milieu, that is younger men and postmenopausal women. Although there have been extensive studies regarding gender difference in MS and its role in cardiovascular diseases [37,38], no studies specifically addressed the role of gender in the association between MS and CKD. Although gender differences in renal disease progression have also been demonstrated in other studies [39,40], the exact mechanisms still remain to be clarified. It is reasonable to attribute the sexual dimorphism in kidney Premenopausea Postmenopausea Totalc Premenopusea Postmenopausea Totalc Premenopusea Postmenopausea Totalc Premenopusea Postmenopausea Totalc Premenopusea Postmenopausea Totalc Premenopusea Postmenopausea Totalc Premenopauseb Postmenopauseb Totald Premenopauseb Postmenopauseb Totald Premenopauseb Postmenopauseb Totald Premenopauseb Postmenopauseb Totald OR (95% CI) 1.343 (0.770, 2.341) 1.909 (1.391, 2.620) 1.432 (1.074, 1.909) 1.320 (0.846, 2.061) 1.320 (0.949, 1.836) 1.197 (1.012, 1.721) 0.787 (0.516, 1.200) 1.143 (0.809, 1.615) 0.901 (0.684, 1.685) 1.284 (0.770, 2.121) 1.536 (1.128, 2.092) 1.392 (1.013, 1.743) 1.477 (0.846, 2.578) 2.218 (1.566, 3.100) 1.497 (1.111, 2.020) 1.341 (0.681, 2.639) 1.381 (0.979, 1.947) 1.372 (1.010, 1.864) OR (95% CI) 1.020 (0.599, 1.737) 1.187 (0.719, 1.958) 0.814 (0.562, 1.179) 1.214 (0.608, 2.424) 1.630 (1.016, 2.546) 1.542 (1.031, 2.077) 1.393 (0.487, 3.968) 2.782 (1.725, 4.487) 2.519 (1.920, 3.521) 2.656 (0.444, 8.401) 2.138 (1.084, 4.216) 2.554 (1.825, 3.274) Fig. 5. Relative risk of chronic kidney disease (CKD) by the number of risk factors of metabolic syndrome (MS). There was a significant graded relationship between the number of risk factors of MS and the corresponding prevalence of CKD in men under the age of 60 years and postmenopausal women (P < 0.05). However, there was no significant association between the number of MS risk factors and the relative risk of CKD in elderly men and premenopausal women. disease, with females protected, to the beneficial vascular actions of the estrogens. Indeed, the rate of progression of renal disease in premenopausal women is slower than in men, and this protection is lost with the onset of menopause and can be restored with oestradiol replacement [41]. Apart from a clear benefit of the presence of oestrogens, there are some situations in which the androgen provides an additional risk. Taken together, the sex difference in the rate of renal disease progression is regarded to be due to both protective estrogens and potentially harmful androgens. Therefore, it can be speculated that the presence of MS may play a role in the development of a decline in GFR in a group of subjects that is already in an unfavourable hormonal status of the kidney such as a lack of oestrogen and/or abundance of androgen. Consistent with this speculation, Zhang et al. showed that oestradiol replacement in ageing rats with MS resulted in an attenuation of proteinuria associated with an increase in renal blood flow and glomerular filtration [42]. This differential association between MS and CKD according to age and gender observed in our cross-sectional study, however, was not confirmed in prospective studies. Two individual studies by Tozawa et al. and Kurella et al. investigating the effect of MS on the development of CKD for 5 or 9 years revealed no gender difference in the relative risk of CKD based on the presence of MS; however, the information regarding sub-analysis based on age, gender and menopausal status of subjects was lacking in their studies [22,43]. Recent worldwide changes in lifestyle, including physical inactivity and unhealthy diet, are likely to have played an important role in the global epidemic of obesity, type 2 diabetes and MS. It is not clear yet whether other lifestylerelated factors such as smoking and alcohol consumption are also associated with MS per se. In our study, there was no significant relationship of MS or CKD with the presence of any of these lifestyle factors or the degree of physical inactivity, smoking or alcohol consumption. Shankar et al. reported a dose-dependent association of smoking with CKD independent of BMI, NSAID use, alcohol consumption, hypertension, diabetes and other confounders in their cohort [44]. They also found an independent association between heavy drinking and CKD. However, there have been other studies showing contradictory results regarding an association between kidney disease and smoking or alcohol consumption, which may be explained by different subject groups with different characteristics [45,46]. This is the first report showing the differential association between MS and CKD according to gender, age and menopausal status. Despite a clear association between MS and CKD, it does not necessarily mean there is a causeand-effect relationship between MS and CKD. Long-term prospective studies may demonstrate the reliable relationship between these conditions, and interventional studies targeting the traits of MS may clarify the putative role of MS on the development of CKD in men and women. The other limitation of our study is a lack of data regarding causes of CKD or duration of MS, which may provide additional information regarding the relationship between MS and CKD. Nevertheless, our study has several strong points. We used the data from the National Health Examination Survey, which ensured a reliable sampling design countrywide and the survey was large scaled and nationally representative, which is different from other studies including the regional population with specific characteristics of participants. In conclusion, MS is an independent determinant for CKD in younger men and postmenopausal women. 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Mina Yu, Dong-Ryeol Ryu, Seung-Jung Kim, Kyu-Bok Choi, Duk-Hee Kang. Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey, Nephrology Dialysis Transplantation, 2010, 469-477, DOI: 10.1093/ndt/gfp483