Vascular endothelial growth factor and uPA/suPAR system in early and advanced chronic kidney disease patients: a new link between angiogenesis and hyperfibrinolysis?

Disturbances in hemostasis and abnormal angiogenesis are components in the plaque growth and destabilization. The role of the vascular endothelial growth factor (VEGF) in the perturbation of hemostasis in chronic kidney disease (CKD) is still unknown. In this preliminary study, we investigate the relation between VEGF and the parameters of coagulation: tissue factor (TF), its inhibitor (TFPI), and fibrinolytic system: urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), plasmin/antiplasmin complexes (PAP) in the patients with mild-to-moderate, and severe CKD and healthy controls. All indices (except TFPI) were raised in CKD patients, particularly in those with severe CKD, compared with controls. The strong positive correlations were between VEGF and some parameters, both coagulation (IF, TFPI, TF/TFPI ratio) and fibrinolytic system (uPA, suPAR, PAP). The relationships were also between the individual hemostatic parameters. In multiple regression analysis, VEGF and kidney dysfunction markers (urea and creatinine levels) were independently associated with uPA, and VEGF was independently associated with suPAR levels. Moreover, PAP was independently associated with age and suPAR. This study represents the first to investigate the relation between VEGF and the activation both coagulation and fibrinolysis in CKD patients. VEGF and the parameters of hemostatic system activation were higher in the CKD group than in the controls with a significant correlation between them. VEGF was independently associated with uPA/suPAR system, whereas suPAR was independently related to PAP levels, suggesting a new link between abnormal angiogenesis and hyperfibrinolysis in this population. (Translational Research 2012;160:346-354)