title: Circulating levels of plasminogen activator inhibitor type-1, tissue plasminogen activator, and thrombomodulin in hemodialysis patients: biochemical correlations and role as independent predictors of coronary artery stenosis.
abstract: This study investigated the relationship between the circulating levels of the endothelial cell glycoproteins plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (TPA), and thrombomodulin (TM) and the major vascular risk factors described in dialysis patients. In addition, the role of these endothelial cell products as independent predictors of coronary artery disease (CAD) was analyzed. Levels of TM, TPA antigen (Ag), TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, thrombin-antithrombin complexes, fibrinopeptide A, C-reactive protein (CRP), interleukin-1beta and tumor necrosis factor-alpha, lipids, apoproteins A1 and B, and albumin were measured in a group of 200 nondiabetic dialysis patients and 100 healthy matched volunteers. When compared with healthy controls, dialysis patients showed increased levels of CRP, TM, TPA, and PAI-1 and evidence of increased thrombin-dependent fibrin formation. Increased levels of active PAI-1 were associated to a great extent with major classic vascular risk factors and to a lesser extent with CRP and serum triglycerides. Forty-six patients (23%) had evidence of CAD. Variables associated with CAD in the univariate analysis included age, time on dialysis, male gender, number of packs of cigarettes per year, high BP, fibrinogen, apolipoprotein B, albumin, PAI-1 activity, CRP, thrombin-antithrombin complexes, and fibrinopeptide A. Logistic regression analysis found age, high-density lipoprotein cholesterol, gender, high BP, CRP, time on dialysis, and PAI-1 activity to be independent predictors of CAD. This model classified correctly 85% of patients as having CAD and showed adequate goodness of fit for all risk categories. Our data support a pathogenic link among activated inflammatory response, endothelial injury, and CAD in hemodialysis patients and suggest that assessment of circulating PAI-1 levels could be an additional tool to identify dialysis patients who are at risk for developing atheromatous cardiovascular disease.
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Segarra
authors.affiliation: Bioquímica, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Chacón
authors.affiliation: CDR Monolab, Hospital Sant Gervasi, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martinez-Eyarre
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Argelaguer
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Vila
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Fort
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Bartolomé
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Camps
authors.affiliation: Unidad de Hemodiálisis, Hospital Sant Gervasi, Barcelona, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Moliner
authors.affiliation: Centro de Nefrología, Virgen de Montserrat, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Pelegrí
authors.affiliation: Centro de Diálisis Nephros, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Marco
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Olmos
authors.affiliation: Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Piera
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003327:Coronary Disease / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D006435:Renal Dialysis; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D010959:Tissue Plasminogen Activator