Clot Structure: A Potent Mortality Risk Factor in Patients on Hemodialysis

[摘要] Patients with CKD on hemodialysis exhibit increased cardiovascular risk. Fibrin clot structure and clot lysis are crucially\n involved in development of cardiovascular events, but little is known about the influence of clot density on outcome in patients\n on hemodialysis. We determined fibrin clot structure parameters and effect on mortality in a prospective cohort of 171 patients\n on chronic hemodialysis (mean\xc2\xb1SD age =59\xc2\xb111 years old; 54% men) using a validated turbidimetric assay. Kaplan\xe2\x80\x93Meier analysis\n revealed that patients on hemodialysis with a denser clot structure had increased all\xe2\x80\x93cause and cardiovascular mortality risks\n (log rank P=0.004 and P=0.003, respectively). Multivariate Cox regression models (adjusted for age, diabetes, sex, and duration of dialysis or fibrinogen,\n C-reactive protein, and complement C3) confirmed that denser clots are independently related to mortality risk. We also purified\n fibrinogen from healthy controls and patients on hemodialysis using the calcium\xe2\x80\x93dependent IF-1 mAb against fibrinogen for\n additional investigation using mass spectrometric analysis and electron microscopy. Whereas purified fibrinogen from healthy\n controls displayed no post-translational modifications, fibrinogen from patients on hemodialysis was glycosylated and guanidinylated.\n Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots\n from fibrinogen of control individuals (mean\xc2\xb1SD =63\xc2\xb12 and 77\xc2\xb12 nm, respectively; P<0.001). In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers, suggesting that difference\n in fiber thickness might be at least partially due to post-translational modifications. Thus, in patients on hemodialysis,\n a denser clot structure may be a potent independent risk factor for mortality.\n

[学科分类] 泌尿医学