Open Access Highly Accessed Research article

Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis

Ruth Dubin1*, Mary Cushman2, Aaron R Folsom3, Linda F Fried4, Walter Palmas5, Carmen A Peralta17, Christina Wassel6 and Michael G Shlipak17

Author Affiliations

1 Dept. of Medicine, Division Nephrology, University of California San Francisco, 521 Parnassus Avenue, Room C443, San Francisco, CA 94143-0532, USA

2 Fletcher Allen Health Care, Thrombosis and Hemostasis Program, Hematology/Oncology Clinic, 111 Colchester Avenue, Burlington, VT 05401, USA

3 Division of Epidemiology & Community Health, 1300 South Second Street, Suite 300 Minneapolis, MN 55454, USA

4 Division of Nephrology, 7E121 VA Pittsburgh Healthcare System, University Drive Center, Pittsburgh, PA, 15240, USA

5 Dept. of Internal Medicine, Columbia University, Presbyterian Hospital, Room 9E-107, 622 West 168th St., New York, NY 10032, USA

6 Dept. of Family and Preventive Medicine, UCSD School of Medicine, 9500 Gilman Drive #0965, La Jolla CA 92093, USA

7 Division of General Internal Medicine, San Francisco VA Medical Center, 4150 Clement St. Rm. 111A1, San Francisco, CA 94143, USA

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BMC Nephrology 2011, 12:3  doi:10.1186/1471-2369-12-3

Published: 26 January 2011



Defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, chronic kidney disease (CKD) is strongly and independently associated with cardiovascular and overall mortality. We hypothesized that reduced kidney function would be characterized by abnormalities of hemostasis.


We tested cross-sectional associations between (eGFR) and multiple hemostatic markers among 6751 participants representing a broad spectrum of kidney function in the Multi-Ethnic Study of Atherosclerosis (MESA). Kidney function was measured using cystatin C (eGFRcys) or creatinine, using CKD Epidemiology Collaboration (eGFRcr). Hemostatic markers included soluble thrombomodulin (sTM), soluble tissue factor (sTF), D-Dimer, von Willebrand factor (vWF), factor VIII, plasmin-antiplasmin complex (PAP), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen. Associations were tested using multivariable linear regression with adjustment for demographics and comorbidities.


In comparison to persons with eGFRcys >90 ml/min/1.73 m2, subjects with eGFRcys < 60 ml/min/1.73 m2 had adjusted levels of sTM, sTF, D-Dimer, PAP, Factor VIII, TFPI, vWF and fibrinogen that were respectively 86%, 68%, 44%, 22%, 17%, 15%, 12% and 6% higher. Subjects with eGFRcys 60-90 ml/min/1.73 m2 had adjusted levels that were respectively 16%, 14%, 12%, 6%, 6%, 6%, 11% and 4% higher (p < 0.05 for all). Percent differences were not significantly different when groups were categorized by eGFRcr.


Throughout a broad spectrum of kidney function, lower eGFR was associated with higher levels of hemostatic markers. Dysregulation of hemostasis may be a mechanism by which reduced kidney function promotes higher cardiovascular risk.