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

Dubin R, Cushman M, Folsom AR, Fried LF, Palmas W, Peralta CA, Wassel C, Shlipak MG - BMC Nephrol (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division Nephrology, University of California San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0532, USA. ruth.dubin@ucsf.edu

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.

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Related in: MedlinePlus

Percent Difference in Biomarker in Groups of eGFR cystatin in MESA*. * Models adjusted for age, race, gender, SES (income), site, current smoking, current alcohol, BMI, prevalent DM, prevalent HTN, statin use, ACE-I, LDL, HDL, TG, fasting glucose, and ln(albumin/creatinine); eGFR cystatin > 90 is the reference group ** p≤0.001 † p≤0.05
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Figure 1: Percent Difference in Biomarker in Groups of eGFR cystatin in MESA*. * Models adjusted for age, race, gender, SES (income), site, current smoking, current alcohol, BMI, prevalent DM, prevalent HTN, statin use, ACE-I, LDL, HDL, TG, fasting glucose, and ln(albumin/creatinine); eGFR cystatin > 90 is the reference group ** p≤0.001 † p≤0.05

Mentions: In addition, we calculated percent differences for each marker between subjects grouped by eGFR, using eGFR > 90 ml/min/1.73 m2 as the reference. The group with eGFRcys <60 ml/min/1.73 m2 had an 86% higher sTM level, 68% higher sTF, 44% higher D-Dimer, 12% higher vWF, 17% higher Factor VIII, 22% higher PAP, 15% higher TFPI, 6.5% higher PAI-1, and 6.3% higher fibrinogen. Participants with eGFR 60-90 ml/min/1.73 m2 had significantly higher levels of all biomarkers ranging from 16% for sTM to 3.8% for fibrinogen. (Figure 1)


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

Dubin R, Cushman M, Folsom AR, Fried LF, Palmas W, Peralta CA, Wassel C, Shlipak MG - BMC Nephrol (2011)

Percent Difference in Biomarker in Groups of eGFR cystatin in MESA*. * Models adjusted for age, race, gender, SES (income), site, current smoking, current alcohol, BMI, prevalent DM, prevalent HTN, statin use, ACE-I, LDL, HDL, TG, fasting glucose, and ln(albumin/creatinine); eGFR cystatin > 90 is the reference group ** p≤0.001 † p≤0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037849&req=5

Figure 1: Percent Difference in Biomarker in Groups of eGFR cystatin in MESA*. * Models adjusted for age, race, gender, SES (income), site, current smoking, current alcohol, BMI, prevalent DM, prevalent HTN, statin use, ACE-I, LDL, HDL, TG, fasting glucose, and ln(albumin/creatinine); eGFR cystatin > 90 is the reference group ** p≤0.001 † p≤0.05
Mentions: In addition, we calculated percent differences for each marker between subjects grouped by eGFR, using eGFR > 90 ml/min/1.73 m2 as the reference. The group with eGFRcys <60 ml/min/1.73 m2 had an 86% higher sTM level, 68% higher sTF, 44% higher D-Dimer, 12% higher vWF, 17% higher Factor VIII, 22% higher PAP, 15% higher TFPI, 6.5% higher PAI-1, and 6.3% higher fibrinogen. Participants with eGFR 60-90 ml/min/1.73 m2 had significantly higher levels of all biomarkers ranging from 16% for sTM to 3.8% for fibrinogen. (Figure 1)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division Nephrology, University of California San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0532, USA. ruth.dubin@ucsf.edu

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.

Show MeSH
Related in: MedlinePlus