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Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals

Linda Fried^*, Cam Solomon, Michael Shlipak, Stephen Seliger, Catherine Stehman-Breen^,||, Anthony J. Bleyer^¶, Paolo Chaves^#, Curt Furberg^**, Lewis Kuller and Anne Newman^,

*Renal Section, VA Pittsburgh Healthcare System, and Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Biostatistics, University of Washington, Seattle, Washington; Medicine Service, Veterans Affairs Medical Center, and Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California; Division of Nephrology, University of Washington, Seattle, Washington; ^||Renal Section, VA Puget Sound Health Care System, Seattle, Washington; ^¶Section of Nephrology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ^#Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, Maryland; **Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; and Division of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Correspondence to Dr. Linda Fried, VA Pittsburgh Healthcare System, University Drive C, Mailstop 111F-U, Pittsburgh, PA 15240. Phone: 412-688-6000 x815930; Fax: 412-688-6908; E-mail: Linda.Fried{at}med.va.gov

Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers—serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin—with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m². Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673