title: Clot Structure: A Potent Mortality Risk Factor in Patients on Hemodialysis.
abstract: Patients with CKD on hemodialysis exhibit increased cardiovascular risk. Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events, but little is known about the influence of clot density on outcome in patients on hemodialysis. We determined fibrin clot structure parameters and effect on mortality in a prospective cohort of 171 patients on chronic hemodialysis (mean±SD age =59±11 years old; 54% men) using a validated turbidimetric assay. Kaplan-Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all-cause and cardiovascular mortality risks (log rankP=0.004 andP=0.003, respectively). Multivariate Cox regression models (adjusted for age, diabetes, sex, and duration of dialysis or fibrinogen, C-reactive protein, and complement C3) confirmed that denser clots are independently related to mortality risk. We also purified fibrinogen from healthy controls and patients on hemodialysis using the calcium-dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy. Whereas purified fibrinogen from healthy controls displayed no post-translational modifications, fibrinogen from patients on hemodialysis was glycosylated and guanidinylated. Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals (mean±SD =63±2 and 77±2 nm, respectively;P<0.001).In vitroguanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers, suggesting that difference in fiber thickness might be at least partially due to post-translational modifications. Thus, in patients on hemodialysis, a denser clot structure may be a potent independent risk factor for mortality.
authors.affiliation: Departments of Internal Medicine I, kschuett@ukaachen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schuett
authors.affiliation: Departments of Internal Medicine I.
authors.forename: Anna
authors.initials: A
authors.lastname: Savvaidis
authors.affiliation: Departments of Internal Medicine I.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maxeiner
authors.affiliation: Departments of Internal Medicine I.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lysaja
authors.affiliation: Institute for Molecular Cardiovascular Research, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Schirmer
authors.affiliation: Center for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Dimkovic
authors.affiliation: Pathology, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.affiliation: Internal Medicine II and.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kaesler
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; and.
authors.forename: Friedo W
authors.initials: FW
authors.lastname: Dekker
authors.affiliation: Internal Medicine II and.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Departments of Internal Medicine I.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.affiliation: Internal Medicine II and.|Medizinisches Versorgungszentrum DaVita Rhein-Ruhr, Düsseldorf, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schlieper
mesh_terms: D005260:Female; D005337:Fibrin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors; D013927:Thrombosis / Q000473:pathology*
chemical_list: D005337:Fibrin
keywords: chronic kidney disease; clot; coagulopathy; dialysis patients; mortality; uremia