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Some lifestyle behaviors and obesity are risk factors for vascular disease, but their relation to kidney disease is uncertain.To determine whether physical inactivity, smoking, alcohol drinking and obesity are associated with the risk of chronic kidney disease, we examined data from a nonconcurrent cohort study of 9,082 U.S. adults, aged 30–74 years, who participated in the second National Health and Nutrition Examination Survey (NHANES II) from 1976 through 1980. By linking the NHANES II Mortality Study with the Medicare end-stage kidney disease registry, we identified 189 incident cases of either treated end-stage kidney disease or chronic kidney disease-related death through 1992.The risk of chronic kidney disease was related to physical inactivity both with and without adjustment for age, sex, race and body-mass index. The adjusted relative risk (RR) of moderately active versus very active persons was 1.2 (95% confidence interval = 0.7–1.8), and of inactive versus very active was 2.2 (1.3–3.8). Risk was also related to smoking; the RR in smokers of 1–20 cigarettes a day versus never smokers was 1.2 (0.7–2.3), and in smokers of more than 20 cigarettes a day, the RR was 2.3 (1.3–4.2). The RR in morbidly obese (body-mass index ≥ 35 kg/m2) compared with normal weight persons was 2.3 (1.1–4.9), but risk was not increased for those classified as overweight or obese. Obesity risk appeared largely mediated by diabetes and hypertension, whereas physical inactivity risk was only partly explained by these factors, and smoking risk was independent of them. Alcohol consumption was not related to chronic kidney disease.These data suggest that physical inactivity, smoking and morbid obesity contribute to the risk of chronic kidney disease.