Association Between Metabolic Syndrome and the Presence of
Kidney Stones in a Screened Population In Gab Jeong, MD, PhD, 1 Taejin Kang, MD, 1 Jeong Kyoon Bang, MD, 1 Junsoo Park, MD, 1 Wansuk Kim, MD, 1 Seung Sik Hwang, MD, PhD, 2 Hong Kyu Kim, MD, PhD, 3 and Hyung Keun Park, MD, PhD 1 Background: Components of metabolic syndrome have been associated with kidney stone disease, but little evidence is available to support a relationship between metabolic syndrome and kidney stone develop- ment in healthy large screened populations. Study Design: Cross-sectional analysis. Setting & Participants: Data were obtained from 34,895 individuals who underwent general health screening tests between January 2006 and December 2006 at the Asan Medical Center. Predictor: Metabolic syndrome was dened according to criteria established by the National Cholesterol Education Program Adult Treatment Panel III, American Heart Association, and National Heart, Lung, and Blood Institute. Outcomes & Measurements: The presence of kidney stones was evaluated using computed tomography or ultrasonography. Results: Of all those screened, 839 (2.4%) had radiologic evidence of kidney stones and metabolic syndrome was diagnosed in 4,779 (13.7%). The multivariable-adjusted ORfor kidney stones increased with an increasing quintile of waist circumference and systolic/diastolic blood pressure (P 0.001). Age, sex, hypertension, and metabolic syndrome status were independent risk factors for kidney stones. The presence of metabolic syndrome had an OR of 1.25 (95% CI, 1.03-1.50) for kidney stone prevalence. In participants with hypertension, the OR for the presence of kidney stones was 1.47 (95% CI, 1.25-1.71) compared with that for participants without hypertension after adjustment for other variables. Limitations: Cross-sectional design, absence of stone composition. Conclusion: Metabolic syndrome is associated with a signicantly increased risk of kidney stone develop- ment. Our ndings suggest the need for interventional studies to test the effects of preventing and treating metabolic syndrome on the risk of kidney stone development. Am J Kidney Dis. 58(3):383-388. 2011 by the National Kidney Foundation, Inc. INDEX WORDS: Kidney calculi; metabolic syndrome X; mass screening. M etabolic syndrome, the simultaneous occur- rence of hyperglycemia, hyperlipidemia, hy- pertension, and visceral obesity, is a chronic disease associated with high mortality. In addition, this condi- tion substantially increases the risk of developing cardiovascular diseases and type 2 diabetes. 1 In the United States, the prevalence of metabolic syndrome is 24% in men and 23.4% in women, increasing at ages 60-69 years to 43.5% in both sexes. 2 In Korea, 19.9% of men and 23.7% of women meet the meta- bolic syndrome criteria established by the National Cholesterol Education ProgramAdult Treatment Panel III (NCEPATP III). 3 Kidney stone disease is common throughout the world, with a lifetime cumulative incidence of symp- tomatic nephrolithiasis ranging from 5%-10%. 4 The prevalence of kidney stones has increased in recent years. In American adults, the lifetime occurrence of kidney stones increased signicantly by 37% in 1976- 1980 and again in 1988-1994. 4 Concurrent with the westernization of Asian culture, kidney stone forma- tion has increased recently in Asian countries. 5 The origin of kidney stones is multifactorial, with epide- miologic studies showing that male sex, race/ethnic- ity, age, climate, occupation, and obesity are associ- ated with kidney stone formation. 6,7 Obesity and components of metabolic syndrome have been associated with nephrolithiasis, 7-12 and several studies have suggested that metabolic syn- drome is linked directly to the formation of kidney stones. 13-15 Although the exact pathophysiologic mechanisms underlying the association between met- abolic syndrome and nephrolithiasis are unclear, met- Fromthe 1 Department of Urology, Asan Medical Center, Univer- sity of Ulsan College of Medicine, Seoul; 2 Department of Social and Preventive Medicine, Inha University School of Medicine, Incheon; and 3 Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Received August 27, 2010. Accepted in revised form March 22, 2011. Originally published online May 27, 2011. Address correspondence to Hyung Keun Park, MD, PhD, Depart- ment of Urology, Asan Medical Center, 388-1 Pungnap 2 dong, Songpa-gu, Seoul 138-736, Korea. E-mail: hkpark@amc.seoul.kr 2011 by the National Kidney Foundation, Inc. 0272-6386/$36.00 doi:10.1053/j.ajkd.2011.03.021 Am J Kidney Dis. 2011;58(3):383-388 383 abolic syndrome has been associated with changes in urinary constituents, including lower urinary pH, de- creased citrate excretion, and increased uric acid and calcium excretion, leading to increased risks of uric acid and calcium stone formation. 13,16,17 To date, little evidence has been available to sup- port a relationship between metabolic syndrome and kidney stone development in healthy screened popula- tions. Preventative health care intervention may be improved by studying the relationship between meta- bolic syndrome and kidney stone formation in a screened population. Determining common modi- able risk factors for the development of kidney stones might uncover newstrategies for treatment and preven- tion. We therefore investigated the association of metabolic syndrome with kidney stone formation in a large screened population. METHODS Study Participants We retrospectively analyzed medical records of 34,895 individu- als who visited the Health Promotion Center of the Asan Medical Center for routine health checkups between January 2006 and December 2006. Our health screening program includes anthropo- metric measurements (height, weight, and waist circumference), blood tests (complete blood cell count, basic chemistry, serologic tests, blood coagulation test, thyroid function tests, and assays for tumor markers), stool/urine analyses, abdominal ultrasonography and/or computed tomography (CT), gastroberscopy, chest radiog- raphy, pulmonary function tests, and electrocardiography. The study protocol was approved by the Institutional Review Board of the Asan Medical Center. Exposure Measures Weight, waist circumference, and blood pressure were measured after an overnight fast, and a blood sample was drawn. Plasma fasting glucose, serum total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were measured using enzy- matic methods with an autoanalyzer (Toshiba 200-FR; Toshiba Medical System Co, Ltd, www.toshiba-medical.co.jp). Metabolic syndrome was dened according to the criteria estab- lished in 2005 by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Asso- ciation, and National Heart, Lung, and Blood Institute. 18 For the criteria for metabolic syndrome, abdominal obesity was dened as waist circumference 90 cm in men and 80 cm in women, according to the World Health Organization Asia-Pacic obesity criteria. 19 Metabolic syndrome was diagnosed in those who satis- ed at least 3 of the following 5 criteria: waist circumference 80 cm in women and 90 cm in men, triglyceride concentration 150 mg/dL or undergoing treatment for hypertriglyceridemia, HDL cholesterol concentration 40 mg/dL in men and 50 mg/dL in women or undergoing treatment for low HDL-C level, blood pressure 130/85 mm Hg or undergoing treatment for hypertension, and fasting plasma glucose level 100 mg/dL or undergoing treatment for hyperglycemia. Outcome Measures The presence of kidney stones was the outcome of our analysis. We retrospectively reviewed radiology records of all participants and recorded kidney stones as present if they were detected using abdominal ultrasonography (n 27,884; IU-22 ultrasound unit; Philips Medical Systems, www.healthcare. philips.com) or CT (n 7,091; SOMATOM Sensation 16; Siemens AG, www.siemens.com/entry/cc/en); stone size did not matter and we even counted cases for which patients did not require treatment. Ultrasonographic examinations were con- ducted by one of several clinically experienced radiologists at our Health Promotion Center, and an ultrasonographic diagno- Table 1. Baseline Demographic Characteristics Characteristics Total No. of Metabolic Syndrome Components Present P 0 1 2 3 4 5 Age (y) 50.0 10.4 46.7 9.9 50.7 9.9 53.0 10.1 53.9 9.9 55.6 10.2 57.4 10.9 Age category 0.001 20-39 y 5,228 (15.0) 3,142 (22.9) 1,196 (11.9) 558 (8.7) 261 (7.7) 62 (5.1) 9 (5.0) 40-49 y 11,438 (32.8) 5,178 (37.8) 3,269 (32.7) 1,815 (28.4) 857 (25.4) 284 (23.4) 35 (19.1) 50-59 y 12,263 (35.1) 4,211 (30.8) 3,787 (37.8) 2,423 (37.8) 1,323 (39.1) 458 (37.7) 61 (33.3) 60 y 5,966 (17.1) 1,169 (8.5) 1,757 (17.6) 1,611 (25.1) 940 (27.8) 411 (33.8) 78 (42.6) Sex 0.001 Male 20,790 (59.6) 6,604 (48.2) 6,419 (64.1) 4,481 (69.9) 2,407 (71.2) 785 (64.6) 94 (51.4) Female 14,105 (40.4) 7,096 (51.8) 3,590 (35.9) 1,926 (30.1) 974 (28.8) 430 (35.4) 89 (48.6) Waist circumference (cm) 80.8 9.0 75.2 7.3 81.3 7.5 85.5 7.5 88.9 7.3 90.9 7.0 92.6 7.1 0.001 Triglycerides (mg/dL) 128.3 84.7 84.2 28.1 121.8 61.6 166.1 96.6 205.5 107.0 244.9 141.3 265.0 114.4 0.001 HDL cholesterol (mg/dL) 56.8 14.1 63.7 13.3 56.3 13.0 51.2 11.8 47.3 10.8 43.7 9.0 38.9 5.8 0.001 Blood pressure (mm Hg) Systolic 117.9 15.5 109.3 10.2 119.5 14.9 125.0 15.3 128.5 15.0 132.7 16.1 135.9 16.3 0.001 Diastolic 74.3 9.5 69.2 6.9 75.3 9.1 78.6 9.1 80.7 9.3 82.7 9.2 82.8 8.7 0.001 Fasting glucose (mg/dL) 97.5 19.4 90.4 8.0 96.3 16.2 102.2 21.6 110.6 28.6 120.7 32.4 135.4 34.9 0.001 Note: Continuous variables given as mean standard deviation; categorical variables are number (percentage). Conversion factors for units: cholesterol in mg/dL to mmol/L, 0.02586; glucose in mg/dL to mmol/L, 0.05551; triglycerides in mg/dL to mmol/L, 0.01129. Abbreviation: HDL, high-density lipoprotein. Am J Kidney Dis. 2011;58(3):383-388 384 Jeong et al sis of kidney stones required demonstration of any hyperechoic structure causing acoustic shadowing. The CT diagnosis of kidney stones was established by visualization of a high- attenuation structure (100 Hounseld units) in the kidney. Statistical Analyses We performed inter-rater reliability analysis using the statistic to determine the agreement between CT and ultrasonography in 7,091 participants who underwent both CT and ultrasonography. The prevalence of metabolic syndrome and individual components thereof and the numbers of metabolic syndrome components present (0, 1, 2, or 3) were determined for the overall study sample. Mean values for continuous demographic and metabolic variables were calculated relative to the presence of kidney stones. The statistical signicance of differences among these variables was assessed using Mann-Whitney U test and 2 test. Crude and multivariable-adjusted odds ratios (ORs) of kidney stone presence were calculated using logistic regression models with age, sex, metabolic syndrome components, and metabolic syndrome status as input factors. The best-tting model was judged according to the Akaike information criterion (AIC), and the model with the lowest AIC was considered to be the best-tting model. The AIC was used to select the most parsimonious model. 20 All P values were 2 tailed, and P 0.05 was dened as statistically signicant. All statistical analysis was performed using Stata, version 10.1 (Stata- Corp). RESULTS Baseline demographic characteristics of the 34,895 participants are listed in Table 1. In the study popula- tion, 59.6% were men and 67.9% were aged 40-59 years. As the number of metabolic syndrome compo- nents increased, waist circumference, triglyceride con- centration, blood pressure, and fasting blood glucose level increased, whereas HDL cholesterol level de- creased. Atotal of 839 participants (2.4% of the population) had radiologic evidence of kidney stones. Of the 7,091 participants who underwent CT and ultrasonog- raphy, 368 (5.2%) had kidney stones detected using CT or ultrasonography. Of the 7,091 participants who underwent both CT and ultrasonography, was 0.78 (P 0.001), for excellent agreement (Table 2). Of 839 participants with kidney stones, a single stone was found in 638 (76.0%); 2 stones, in 107 (12.8%); 3 stones, in 53 (6.3%); 4 stones, in 38 (4.5%); and 5 stones, in 3 participants (0.4%). Mean number of kidney stones per person was 1.4. Mean kidney stone size was 6.5 mm (median, 6; range, 1-27). Character- istics of kidney stones by the number of metabolic syndrome component fullled are listed in Table 3. As the number of metabolic syndrome components in- creased, the frequency of kidney stones increased regardless of the diagnostic test used. Overall, 4,779 (13.7%) participants were given a diagnosis of metabolic syndrome. The criterion for increased blood pressure was fullled in 30.5% of participants and was the most common of the 5 metabolic syndrome components (increased triglycer- ides, 27.2%; increased waist circumference, 24.2%; low HDL cholesterol, 15.4%; and impaired glucose tolerance, 13.7%). A total of 61% of participants fullled at least one criterion of metabolic syndrome. Table 4 lists crude and multivariable-adjusted ORs for kidney stones according to quintile of the 5 meta- bolic syndrome components. Crude and multivariable- adjusted ORs for kidney stones increased with increas- ing quintile of waist circumference (P 0.001) and systolic and diastolic blood pressure (P 0.001 and P 0.001, respectively). When each of the 5 meta- Table 2. Agreement Between Diagnostic Tests for the Detection of Kidney Stones in Participants Who Had Both CT and US Kidney Stone on US Total Yes No Kidney stone on CT Yes 239 (3.3) 20 (0.3) 259 (3.6) No 109 (1.6) 6,723 (94.8) 6,832 (96.4) Total 348 (4.9) 6,743 (95.1) 7,091 (100) Note: N 7,091. Values shown are number (percentage). Abbreviations: CT, computed tomography; US, ultrasonogra- phy. Table 3. Characteristics of Kidney Stone by Number of Metabolic Syndrome Components Fullled Characteristics Total No. of Metabolic Syndrome Components Present P 0 1 2 3 4 5 No. of participants 34,895 13,700 10,009 6,407 3,381 1,215 183 Presence of kidney stone by diagnostic test Total 839 (2.4) 240 (1.8) 245 (2.4) 177 (2.8) 131 (3.9) 38 (3.1) 8 (4.4) 0.001 Detected by US 675 (1.8) 198 (1.8) 191 (2.4) 137 (2.7) 112 (4.1) 31 (3.3) 6 (4.2) 0.001 Detected by CT 164 (1.5) 42 (1.5) 54 (2.7) 40 (3.1) 19 (3.0) 7 (2.5) 2 (5.1) 0.001 No. of kidney stones per person 1.4 0.8 1.4 0.8 1.4 0.8 1.4 0.8 1.4 0.7 1.4 1.0 1.4 0.8 0.9 Size of the largest kidney stone (mm) 6.5 3.1 6.5 3.0 6.5 2.9 6.6 3.8 6.0 2.1 5.9 2.5 6.4 2.0 0.8 Note: Categorical variables are shown as number (percentage), continuous variables as mean standard deviation. Abbreviations: CT, computed tomography; US, ultrasonography. Am J Kidney Dis. 2011;58(3):383-388 385 Metabolic Syndrome and Kidney Stone bolic components was analyzed as a continuous vari- able, systolic and diastolic blood pressure (P 0.001 and P 0.001, respectively), waist circumference (P 0.001), and triglyceride concentration (P 0.02) were independent risk factors for kidney stones after adjustment for age and sex. HDL cholesterol and fasting blood glucose levels were not associated inde- pendently with risk of kidney stones (P 0.3 and P 0.7, respectively). Table 5 lists crude and multivariable-adjusted ORs of kidney stone presence associated with age, sex, hypertension, and metabolic syndrome status. We selected this as the best-tting model because it had the lowest AIC value. Age was signicantly positively associated with the OR for kidney stone development. The presence of metabolic syndrome (3 criteria) was associated with a 71% increased OR of kidney stone prevalence compared with the absence of meta- bolic syndrome. After adjustment for age, sex, and the presence of hypertension, this OR decreased to 1.25 (95% condence interval [CI], 1.03-1.50). Compared with men, women had a multivariable OR for the presence of kidney stones of 0.56 (95% CI, 0.48- 0.65). In participants with hypertension, the OR for the presence of kidney stones was 1.47 (95% CI, 1.25-1.71) compared with those without hypertension Table 4. Crude and Multivariable-Adjusted ORs for Kidney Stone by Quintile of the 5 Metabolic Syndrome Components Total No. Cases of Stones No. (%) Crude OR (95% CI) P Adjusted OR (95% CI) a P Waist circumference 0.001 0.001 Quintile 1 (72 cm) 7,024 100 (1.4) 1.00 (reference) 1.00 (reference) Quintile 2 (73-78 cm) 7,946 142 (1.8) 1.26 (0.97-1.63) 0.98 (0.75-1.28) Quintile 3 (79-83 cm) 7,536 185 (2.5) 1.74 (1.36-2.23) 1.13 (0.86-1.49) Quintile 4 (84-88 cm) 5,510 178 (3.2) 2.31 (1.80-2.96) 1.42 (1.07-1.89) Quintile 5 (89 cm) 6,879 234 (3.4) 2.44 (1.93-3.09) 1.48 (1.12-1.95) Triglycerides 0.001 0.2 Quintile 1 (69 mg/dL) 6,994 138 (2.0) 1.00 (reference) 1.00 (reference) Quintile 2 (70-92 mg/dL) 6,955 129 (1.9) 0.94 (0.74-1.20) 0.79 (0.62-1.01) Quintile 3 (93-122 mg/dL) 6,991 186 (2.7) 1.36 (1.09-1.70) 1.06 (0.85-1.33) Quintile 4 (123-170 mg/dL) 6,967 180 (2.6) 1.31 (1.05-1.65) 0.97 (0.77-1.22) Quintile 5 (171 mg/dL) 6,988 206 (3.0) 1.51 (1.22-1.88) 1.07 (0.86-1.35) HDL cholesterol 0.001 0.2 Quintile 1 (44 mg/dL) 7,080 212 (3.0) 1.00 (reference) 1.00 (reference) Quintile 2 (45-51 mg/dL) 6,893 174 (2.5) 0.84 (0.69-1.03) 0.89 (0.73-1.09) Quintile 3 (52-58 mg/dL) 6,984 169 (2.4) 0.80 (0.66-0.99) 0.90 (0.73-1.10) Quintile 4 (59-67 mg/dL) 6,962 146 (2.1) 0.69 (0.56-0.86) 0.84 (0.68-1.04) Quintile 5 (68 mg/dL) 6,976 138 (2.0) 0.65 (0.53-0.81) 0.88 (0.70-1.10) Systolic BP 0.001 0.001 Quintile 1 (105 mm Hg) 7,466 113 (1.5) 1.00 (reference) 1.00 (reference) Quintile 2 (106-113 mm Hg) 7,138 161 (2.3) 1.50 (1.18-1.91) 1.27 (0.99-1.62) Quintile 3 (114-120 mm Hg) 6,476 148 (2.3) 1.52 (1.19-1.95) 1.19 (0.93-1.53) Quintile 4 (121-130 mm Hg) 7,171 202 (2.8) 1.89 (1.50-2.38) 1.40 (1.10-1.78) Quintile 5 (131 mm Hg) 6,644 215 (3.2) 2.18 (1.73-2.74) 1.58 (1.25-2.01) Diastolic BP 0.001 0.001 Quintile 1 (66 mm Hg) 7,326 117 (1.6) 1.00 (reference) 1.00 (reference) Quintile 2 (67-71 mm Hg) 6,888 148 (2.2) 1.35 (1.06-1.73) 1.15 (0.90-1.48) Quintile 3 (72-76 mm Hg) 7,170 152 (2.1) 1.33 (1.05-1.70) 1.07 (0.84-1.37) Quintile 4 (77-82 mm Hg) 6,939 189 (2.7) 1.72 (1.37-2.18) 1.31 (1.03-1.66) Quintile 5 (83 mm Hg) 6,572 233 (3.6) 2.27 (1.81-2.84) 1.64 (1.30-2.07) Fasting glucose 0.001 0.1 Quintile 1 (85 mg/dL) 6,992 137 (2.0) 1.00 (reference) 1.00 (reference) Quintile 2 (86-91 mg/dL) 7,098 139 (2.0) 1.00 (0.91-1.44) 0.89 (0.70-1.13) Quintile 3 (92-96 mg/dL) 6,973 156 (2.2) 1.15 (0.91-1.44) 0.94 (0.74-1.19) Quintile 4 (97-103 mg/dL) 6,903 196 (2.8) 1.46 (1.17-1.82) 1.12 (0.89-1.40) Quintile 5 (104 mg/dL) 6,929 211 (3.1) 1.57 (1.26-1.95) 1.09 (0.87-1.37) Note: Conversion factors for units: cholesterol in mg/dL to mmol/L, 0.02586; glucose in mg/dL to mmol/L, 0.05551; triglycerides in mg/dL to mmol/L, 0.01129. Abbreviations: BP, blood pressure; CI, condence interval; HDL, high-density lipoprotein; OR, odds ratio. a Adjusted for age and sex. Am J Kidney Dis. 2011;58(3):383-388 386 Jeong et al after adjustment for other variables. The diagnostic test for detecting kidney stones was not associated signicantly with the detection of kidney stones (crude OR, 0.94 for CT vs ultrasonography; 95% CI, 0.79- 1.12; P 0.5). After adjustment for age, sex, hyper- tension, and the presence of metabolic syndrome, diagnostic testing was not associated with the OR of the presence of kidney stones (multivariable-adjusted OR, 0.95; 95% CI, 0.80-1.12; P 0.5). DISCUSSION In our large screened population, metabolic syn- drome was associated with a signicantly increased risk of kidney stone presence after adjustment for other confounding variables. We also showed that metabolic syndrome is associated with risk of kidney stones in addition to already known independent met- abolic risk factors, such as hypertension. Our results are consistent with those of an earlier study, which found a signicant association between metabolic syndrome and echographic evidence of nephrolithia- sis in an inpatient white population referred to the hospital for any reason. 14 However, our present study is the rst to show such an association in a large screened population of healthy Asian men. Although the detailed mechanisms responsible for the association of metabolic syndrome with kidney stone development are unclear, the syndrome has been associated with a self-reported history of kidney stones. In a study of 14,870 participants in the Third National Health and Nutrition Examination Survey (NHANES III), the presence of 4-5 traits of metabolic syndrome was associated with an approximately 2-fold increase in self-reported kidney stone disease. 15 We also found that hypertension was associated positively with risk of kidney stones after adjustment for patient age, sex, and the presence of metabolic syndrome. Compared with normotensive patients, the multivariable OR for kidney stones in hypertensive patients was 1.47. To date, several epidemiologic studies have analyzed the association between hyper- tension and nephrolithiasis. In cross-sectional studies, it has been reported that nephrolithiasis is more fre- quent in hypertensive patients than in those who are normotensive, but the pathologic link between hyper- tension and stone disease remains to be claried. 21-24 In addition, some prospective studies reported the risk of stones in hypertensive patients. 10,22,25 Although previous studies have suggested that the prevalence of kidney stones is amplied by diabetes mellitus, especially in those with uric acid nephrolithia- sis, our data do not support a possible association between diabetes and kidney stones. 8,26,27 In our study, fasting blood glucose level, which was ana- lyzed as either a categorical or continuous variable, was not an independent risk factor for kidney stones after adjustment for patient age and sex. It is difcult to directly compare our results with those of studies conducted in Western countries. Differences in racial/ ethnic variables, age distribution, frequency of neph- rolithiasis, methods of detection of nephrolithiasis (ie, electronic data based or self-reported questionnaires vs a radiologic diagnosis), and study populations may have affected results of analyses. Therefore, addi- Table 5. Crude and Multivariable-Adjusted ORs of the Association Between Kidney Stone Presence and Metabolic Syndrome Status Total No. Cases of Stones No. (%) Crude OR (95% CI) P Adjusted OR (95% CI) a P Age category 20-39 y 5,163 65 (1.2) 1.00 (reference) 1.00 (reference) 40-49 y 11,209 229 (2.0) 1.62 (1.23-2.14) 0.001 1.50 (1.14-1.98) 0.004 50-59 y 11,896 367 (3.0) 2.45 (1.88-3.20) 0.001 2.13 (1.63-2.79) 0.001 60 y 5,788 178 (2.4) 2.44 (1.83-3.25) 0.001 1.96 (1.46-2.63) 0.001 Sex Male 20,171 619 (3.0) 1.00 (reference) 1.00 (reference) Female 13,885 220 (1.6) 0.52 (0.44-0.60) 0.001 0.56 (0.48-0.65) 0.001 Hypertension No 23,779 465 (1.9) 1.00 (reference) 1.00 (reference) Yes 10,277 374 (3.5) 1.86 (1.62-2.14) 0.001 1.47 (1.25-1.71) 0.001 Metabolic syndrome No 29,454 662 (2.2) 1.00 (reference) 1.00 (reference) Yes 4,602 177 (3.7) 1.71 (1.45-2.03) 0.001 1.25 (1.03-1.50) 0.02 Note: Criteria for metabolic syndrome were used as dened by the National Cholesterol Education Program Adult Treatment Panel III, American Heart Association, National Heart, Lung, and Blood Institute statement. 18 Abbreviations: CI, condence interval; OR, odds ratio. a Multivariable adjusted. Am J Kidney Dis. 2011;58(3):383-388 387 Metabolic Syndrome and Kidney Stone tional studies are needed to determine whether diabe- tes is an independent risk factor for the formation of calcium stones. Our ndings have important implications for clini- cal care and public health because metabolic syn- drome is so common. If metabolic syndrome and the presence of kidney stones are associated, stone devel- opment may be prevented by lifestyle modication and subsequent resolution of metabolic syndrome. Our study was strengthened by the large size of the screened cohort population and the use of standard- ized clinical and laboratory covariates. However, the study was limited by our inability to measure and analyze stone composition. In addition, it was difcult to dene the duration of any metabolic risk factor because a substantial number of individuals with such risk factors may be undiagnosed and the duration of risk factors may reect the extent of medical surveil- lance. 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