Thrombin generation and endothelial dysfunctional markers in different stages of nephrotic syndrome

Abstract

Objectives: Venous thromboembolism is an important and potentially life-threatening complication of nephrotic syndrome (NS). This study aims to evaluate the functional test of thrombin generation (TG) in different stages of NS; determine its relation with the coagulation screening tests (prothrombin time [PT] and activated partial thromboplastin time), hemostatic activation markers (thrombin–antithrombin complex [TAT] and prothrombin fragment 1+2 [PF1+2]), and von Willebrand factor (vWF) and its proteolytic enzyme ADAMTS-13; and determine the correlation between TG and NS severity, as reflected by the levels of proteinuria and albumin. Materials and Methods: This case–control cross-sectional study included 125 patients (n = 40, nephrotic range proteinuria; n = 45, NS; n = 40, remission) and 80 controls. Calibrated automated thrombogram assay (endogenous thrombin potential [ETP]) was performed to determine TG. TAT, PF1+2, vWF, and ADAMTS-13 were measured using enzyme-linked immunosorbent assay. Results: TG (ETP), TAT, PF1+2, and vWF levels were significantly higher in all of the patient groups (P < 0.0001) than in the control group. ADAMTS-13 levels were significantly lower in the NS group (P < 0.0001) than in the control group. Conclusion: Our findings confirm activation of the coagulation pathway in nephrotic patients. However, the degree of hypercoagulopathy (especially TG [ETP]) is positively correlated with proteinuria. Proteinuria could be considered an indirect indicator of the highest risk of thrombotic disease in patients with NS.

Keywords

• Nephrotic syndrome
• proteinuria
• thrombin generation
• thrombophilia