Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis.
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.
Department of Medicine, Division Nephrology, University of California San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0532, USA. ruth.dubin@ucsf.edu
Ruth
R
Dubin
Mary
M
Cushman
Aaron R
AR
Folsom
Linda F
LF
Fried
Walter
W
Palmas
Carmen A
CA
Peralta
Christina
C
Wassel
Michael G
MG
Shlipak
D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000032:analysis*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D013223:Statistics as Topic; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D001779:Blood Coagulation Factors
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