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

Abstract

BackgroundDefined 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.MethodsWe 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.ResultsIn 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.ConclusionsThroughout 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.

Serum D-Dimer Concentrations in Nephrotic Syndrome Track with Albuminuria, Not Estimated Glomerular Filtration Rate

“…A cross-sectional analysis of the Multi Ethnic Study of Atherosclerosis [11] found that D-dimer was moderately associated with eGFR using the CKD EPI equation, with levels increasing by 5% for every 10 ml/min/1.73 m 2 reduction in eGFR [11]. However, this study did not address urinary protein excretion or serum albumin [11. ]…”

“…Our hypothesis was that proteinuria might be associated with enhanced hepatic synthesis of fibrinogen in a similar manner to serum cholesterol in the nephrotic syndrome and hence D-dimer elevation. Although previous studies have alluded to the relationship between reduced kidney function and D-dimer level [11], the relationship between proteinuria and D-dimer levels has not been thoroughly described. Secondly, we followed each patient in this cohort prospectively for 2 years to assess the incidence of thrombosis in those with and without elevated D-dimer levels at baseline.…”

Kidney Function Decline in the Elderly: Impact of Lipoprotein-Associated Phospholipase A₂

“…We found that inflammation did not attenuate our findings. Since the direction of the association between inflammation and kidney disease remains unclear [5,6], future studies on the interplay between Lp-PLA 2 , inflammation, and kidney function decline are warranted.…”

“…Proposed mechanisms to explain these associations have included increased inflammation or oxidative stress associated with vascular damage. However, the associations of inflammatory markers and kidney function are modest, and the direction of the association remains unclear [5,6,7]. …”

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients

“…1 Due to the significant increase in cardiovascular morbidity and mortality in dialyzed patients, 2,3 more attention has been paid to the role of thrombogenic factors in the pathogenesis of cardiovascular events in uremia. 4 Disturbances in hemostasis are common complications of kidney diseases.…”