BACKGROUND: Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease. METHODS: Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate >= 60 mL/min/1.73 m(2) without micro- or macroalbuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II to III obesity were defined as a BMI of 18.5 to 24.9 kg/m(2), 25.0 to 29.9 kg/m(2), 30.0 to 34.9 kg/m(2), and >= 35.0 kg/m(2), respectively. Elevated serum cystatin C was defined as >= 1.09 mg/L (>= 99th percentile for participants 20-39 years of age without diabetes, hypertension, micro-or macroalbuminuria, or stage 3-5 chronic kidney disease). RESULTS: The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II to III obesity, respectively (P trend < .001). After multivariate adjustment for demographics, behaviors, systolic blood pressure, and serum biomarkers, and compared with participants of normal weight, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02-2.10) for overweight, 2.36 (1.56-3.57) for class I obesity, and 2.82 (1.56-5.11) for class II to III obesity. CONCLUSION: A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably affects elevated serum cystatin C and the development of chronic kidney disease. (C) 2008 Elsevier Inc. All rights reserved.