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Kidney Function as a Predictor of Noncardiovascular Mortality

Linda F. Fried^*, Ronit Katz, Mark J. Sarnak, Michael G. Shlipak, Paulo H.M. Chaves^||, Nancy Swords Jenny^¶, Catherine Stehman-Breen^#, Dan Gillen^**, Anthony J. Bleyer, Calvin Hirsch, David Siscovick and Anne B. Newman^||||

^* VA Pittsburgh Healthcare System and Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Collaborative Health Studies Coordinating Center, University of Washington, Seattle, Washington; Division of Nephrology, Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts; General Internal Medicine Section, Veterans Affairs Medical Center and Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco, California; ^|| Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, Maryland; ^¶ Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont; ^# Amgen, Thousand Oaks, California; ^** Department of Statistics, University of California, Irvine, Irvine, California; Section of Nephrology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Departments of Medicine and Public Health Sciences, University of California, Davis Medical Center, Sacramento, CA; Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington; ^|||| Department of Epidemiology, University of Pittsburgh Graduate School of Public Health and Division of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Address correspondence to: Dr. Linda Fried, VA Pittsburgh Healthcare System, University Drive C, Mailstop 111F-U, Pittsburgh, PA 15240. Phone: 412-688-6181; Fax: 412-688-6908; E-mail: linda.fried{at}med.va.gov

Received for publication April 11, 2005. Accepted for publication September 13, 2005.

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

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