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Dena E. Rifkin, MD; Michael G. Shlipak, MD, MPH; Ronit Katz, DPhil; Linda F. Fried, MD, MPH; David Siscovick, MD, MPH; Michel Chonchol, MD; Anne B. Newman, MD; Mark J. Sarnak, MD, MS

Arch Intern Med. 2008;168(20):2212-2218.

Background  Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults.

Methods  The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR_creat) and cystatin C (eGFR_cys) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m² per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up.

Results  Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR_creat and eGFR_cys were 79 (23) mL/min/1.73 m² and 79 (19) mL/min/1.73 m², respectively. Individuals with rapid decline measured by eGFR_creat (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR_cys (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease.

Conclusion  Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.

Author Affiliations: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts (Drs Rifkin and Sarnak); General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, and Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco (Dr Shlipak); Collaborative Health Studies Coordinating Center, University of Washington, Seattle (Dr Katz); Renal Section, Medical Service, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (Dr Fried); Departments of Epidemiology and Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh (Drs Fried and Newman); Departments of Medicine and Epidemiology, University of Washington, Seattle (Dr Siscovick); and Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver (Dr Chonchol).

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