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Results From the Kidney Early Evaluation Program (KEEP)

Peter A. McCullough, MD, MPH; Claudine T. Jurkovitz, MD; Pablo E. Pergola, MD, PhD; Janet B. McGill, MD; Wendy W. Brown, MD; Alan J. Collins, MD; Shu-Cheng Chen, MS; Suying Li, PhD; Ajay Singh, MD; Keith C. Norris, MD; Michael J. Klag, MD; George L. Bakris, MD; for the KEEP Investigators

Arch Intern Med. 2007;167(11):1122-1129.

Background  The relationships of anemia, microalbuminuria, and estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) and subsequent death are not fully understood. We hypothesized that each of these chronic kidney disease–related measures would have an independent relationship with CVD.

Methods  A cohort of 37 153 persons screened in the National Kidney Foundation's Kidney Early Evaluation Program were followed up for a median of 16.0 months (range, 0.2-47.5 months). Participants were volunteers who completed surveys regarding past medical events and who underwent blood pressure and laboratory testing. Estimated glomerular filtration rate was computed using a 4-variable equation. Mortality was ascertained by linkage to national data systems.

Results  Of 37 153 persons, the mean ± SD age was 52.9 ± 15.9 years, and 68.7% were female. A total of 1835 (4.9%) had a self-reported history of myocardial infarction, 1336 (3.6%) had a history of stroke, and 2897 (7.8%) had a history of myocardial infarction or stroke. Multivariate analysis controlling for age demonstrated that the following were independently associated with CVD: male sex (odds ratio [OR], 1.64; P<.001), smoking (OR, 1.73; P<.001), body mass index (OR, 1.01; P = .03), diabetes mellitus (OR, 1.66; P<.001), hypertension (OR, 1.77; P<.001), eGFR of 30 to 59 mL/min per 173 m³ (OR, 1.37; P = .001), hemoglobin level of 12.8 g/dL or less (OR, 1.45; P<.001), and microalbuminuria of greater than 30 mg/L (OR, 1.28; P = .01). Survival analysis found CVD (OR, 3.02; P = .003), chronic kidney disease (OR, 1.98; P = .05), and the combination (OR, 3.80; P<.001) to be independent predictors of mortality. Persons with a combination of all 3 chronic kidney disease measures (anemia, microalbuminuria, and eGFR of <60 mL/min per 1.73 m²) had the lowest survival of about 93% by the end of 30 months.

Conclusion  Anemia, eGFR, and microalbuminuria were independently associated with CVD, and when all 3 were present, CVD was common and survival was reduced.

Author Affiliations: Divisions of Cardiology, Nutrition, and Preventive Medicine, Department of Medicine, William Beaumont Hospital, Royal Oak, Mich (Dr McCullough); Center for Outcomes Research, Christiana Care Health System, Newark, Del (Dr Jurkovitz); Division of Nephrology, Department of Medicine, The University of Texas Health Science Center, San Antonio (Dr Pergola); Division of Endocrinology, Department of Medicine, Washington University School of Medicine, St Louis, Mo (Dr McGill); Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Ill (Dr Brown); Division of Nephrology, Department of Medicine, USRDS Coordinating Center, Minneapolis, Minn (Drs Collins and Li and Mr Chen); Division of Nephrology, Department of Medicine, Brigham and Women's Hospital, Boston, Mass (Dr Singh); Department of Medicine, Charles R. Drew University of Medicine and Science, Lynwood, Calif (Dr Norris); The Johns Hopkins Bloomberg School of Public Health, Baltimore, Md (Dr Klag); and Divisions of Preventive Medicine, Hypertension, and Nephrology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago (Dr Bakris).
Group Information: A complete list of the KEEP Investigators was published in KEEP 2005 Annual Data Report, New York, NY: National Kidney Foundation; 2005:s8.

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