Alterations in Coagulation and Endothelial Function in Nephrotic Syndrome: A Multi-Center, Cross-Sectional Analysis.

Background: Nephrotic syndrome is associated with an increased risk of venous thromboembolism, but the underlying mechanism remains incompletely understood. The efficacy of prophylactic anticoagulant strategies is also poorly documented. To optimize preventive therapy, this study aimed to characterize the coagulation abnormalities in patients with nephrotic syndrome.

Methods: This Danish multicenter, cross-sectional study included 47 adult patients with nephrotic syndrome, defined by plasma-albumin < 30g/L and urine albumin-creatinine ratio >2200mg/g. Exclusion criteria included estimated glomerular filtration rate < 30 mL/min/1.73m2, ongoing anticoagulant treatment, thrombophilia, prior thrombosis, malignancy, or pregnancy. Markers of endothelial cell function, platelet function, thrombin generation and fibrinolysis were compared to those of healthy individuals (n ranging from 10 to 174 depending on assay).

Results: Patients with nephrotic syndrome (n = 47) had significantly increased thrombin generation markers compared to healthy individuals, as indicated by elevated prothrombin fragment 1+2 (509 pmol/L, 95% CI 426-592 vs. 183 pmol/L, 95% CI 171-196; p <0.001) and thrombin-antithrombin complex (3.5 µg/L, 95% CI 3.2-3.8 vs. 2.5 µg/L, 95% CI 2.3-2.7; p <0.001). Fibrinolysis was impaired, as demonstrated by prolonged 50% clot lysis time (1281 s, 95% CI 1101-1462 vs.: 964 s, 95% CI 843-1085; p = 0.004). Endothelial cell markers, including thrombomodulin, syndecan-1, and von Willebrand factor, were significantly elevated. In contrast, platelet function, natural anticoagulants, and other coagulation markers did not differ.

Conclusions: Our results indicate that the prothrombotic state in nephrotic syndrome is driven by excessive thrombin generation and impaired fibrinolysis rather than increased platelet aggregation. In line with current guideline recommendations, this supports the rationale for antithrombotic strategies targeting secondary hemostasis rather than platelet function in patients with nephrotic syndrome.