Predictors of New-Onset Kidney Disease in a Community-Based Population

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

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).

Corresponding Author: Caroline S. Fox, MD, MPH, Framingham Heart Study, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702 ([email protected]).

Author Contributions: Dr Fox had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Fox, Larson, Culleton, Levy.

Acquisition of data: Wilson.

Analysis and interpretation of data: Fox, Larson, Leip, Wilson, Levy.

Drafting of the manuscript: Fox.

Critical revision of the manuscript for important intellectual content: Larson, Leip, Culleton, Wilson, Levy.

Statistical expertise: Larson, Leip.

Obtained funding: Larson, Wilson.

Administrative, technical, or material support: Fox, Wilson.

Study supervision: Levy.

Funding/Support: The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195).

Role of the Sponsor: The National Heart, Lung, and Blood Institute participated in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, and approval of the manuscript.

Acknowledgment: We thank Josef Coresh, MD, PhD, for his aid in preparation of the manuscript.

JAMA: The Journal of the American Medical Association 291(7):p 844-850, February 18, 2004.

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.