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Caroline S. Fox, MD, MPH; Martin G. Larson, ScD; Eric P. Leip, MS; Bruce Culleton, MD; Peter W. F. Wilson, MD; Daniel Levy, MD

JAMA. 2004;291:844-850.

Context  Kidney disease is associated with an increased risk for the development of cardiovascular disease and end-stage renal disease; however, risk factors for kidney disease have not been well studied.

Objective  To identify predictors of the development of new-onset kidney disease.

Design, Setting, and Participants  A community-based, longitudinal cohort study of 2585 participants who attended both a baseline examination in 1978-1982 and a follow-up examination in 1998-2001, and who were free of kidney disease at baseline.

Main Outcome Measures  Kidney disease was assessed by the Modification of Diet in Renal Disease Study equation and defined by a glomerular filtration rate (GFR) in the fifth or lower percentile (59.25 mL/min per 1.73 m² in women, 64.25 mL/min per 1.73 m² in men). Stepwise logistic regression was used to determine the impact of risk factors on the occurrence of new-onset kidney disease. Baseline and long-term, 12-year, averaged risk factor models were explored.

Results  At baseline, there were 1223 men and 1362 women, with a mean age of 43 years, who were free of preexisting kidney disease. After a mean follow-up of 18.5 years, 244 participants (9.4%) had developed kidney disease. In multivariable models, baseline age (odds ratio [OR], 2.36 per 10-year increment; 95% confidence interval [CI], 2.00-2.78), GFR (<90 mL/min per 1.73 m²: OR, 3.01; 95% CI, 1.98-4.58; 90-119 mL/min per 1.73 m²: OR, 1.84; 95% CI, 1.16-2.93), body mass index (OR, 1.23 per 1 SD; 95% CI, 1.08-1.41), diabetes (OR, 2.60; 95% CI, 1.44-4.70), and smoking (OR, 1.42; 95% CI, 1.06-1.91) were related to the development of kidney disease. In addition to baseline age and GFR, the long-term, averaged risk factors that were predictive of kidney disease included hypertension (OR, 1.57; 95% CI, 1.17-2.12), high-density lipoprotein cholesterol level (OR, 0.80 per 1 SD; 95% CI, 0.69-0.92), and diabetes (OR, 2.38; 95% CI, 1.45-3.92). Compared with a normal GFR (120 mL/min per 1.73 m²), a mildly reduced GFR (<90 mL/min per 1.73 m²) predicted a 3-fold odds of progression to kidney disease (OR, 2.95; 95% CI, 1.94-4.49).

Conclusions  Established cardiovascular disease risk factors are associated with the development of new-onset kidney disease. Patients with a mildly reduced GFR should be monitored for progression to kidney disease.

Author Affiliations: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass, and National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (Drs Fox and Levy); Boston University School of Medicine, Boston, Mass (Drs Larson, Wilson, and Levy, and Mr Leip); and University of Calgary Foothills Hospital, Calgary, Alberta (Dr Culleton).

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