Overweight, obesity, and the development of stage 3 CKD: The Framingham Heart Study

Background: Prior research yielded conflicting results about the magnitude of the association between body mass index (BMI) and chronic kidney disease (CKD). Study Design: Prospective cohort study. Settings & Participants: Framingham Offspring participants (n = 2,676; 52% women; mean age, 43 years) free of stage 3 CKD at baseline who participated in examination cycles 2 (1978-1981) and 7 (1998-2001). Predictor: BMI. Outcome: Stage 3 CKD (estimated glomerular filtration rate < 59 mL/min/1.73 m(2) for women and < 64 mL/min/1.73 m(2) for men). Measurements: Age-, sex-, and multivariable-adjusted (diabetes, systolic blood pressure, hypertension treatment, current smoking status, and high-density lipoprotein cholesterol level) logistic regression models were used to examine the relationship between BMI at baseline and incident stage 3 CKD and incident dipstick proteinuria (trace or greater). Results: At baseline, 36% of the sample was overweight and 12% was obese; 7.9% (n = 212) developed stage 3 CKD during 18.5 years of follow-up. Relative to participants with normal BMI, there was no association between overweight individuals and stage 3 CKD incidence in age- and sex-adjusted models (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.93 to 1.81; P = 0.1) or multivariable models (OR, 1.06; 95% CI, 0.75 to 1.50; P = 0.8). Obese individuals had a 68% increased odds of developing stage 3 CKD (OR, 1.68; 95% CI, 1.10 to 2.57; P = 0.02), which became nonsignificant in multivariable models (OR, 1.09; 95% CI, 0.69 to 1.73; P = 0.7). Similar findings were observed when BMI was modeled as a continuous variable or quartiles. Incident proteinuria occurred in 14.4%; overweight and obese individuals were at increased odds of proteinuria in multivariable models (OR, 1.43; 95% CI, 1.09 to 1.88; OR, 1.56; 95% CI, 1.08 to 2.26, respectively). Limitations: BMI is measure of generalized obesity and not abdominal obesity. Participants are predominantly white, and these findings may not apply to different ethnic groups. Conclusions: Obesity is associated with increased risk of developing stage 3 CKD, which was no longer significant after adjustment for known cardiovascular disease risk factors. The relationship between obesity and stage 3 CKD may be mediated through cardiovascular disease risk factors.