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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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.