Hypercoagulability risk factors associated with venous thromboembolic events in patients with idiopathic membranous nephropathy and nephrotic syndrome: a prospective observational study

Background: The nephrotic syndrome (NS) is associated with an increased incidence of thromboembolic complications due to multiple abnormalities in haemostasis and the coagulation system occurring in these patients. We aimed to assess prospectively the risk of venous thromboembolic events (VTE) in a large cohort of NS patients and to identify predictive factors for VTE, especially haemostasis-related parameters. Methods: We performed a prospective observational study including consecutive adult patients with idiopathic membranous nephropathy and NS. The diagnosis of NS was confirmed by the presence of a daily protein excretion greater than 3.5 g. Clinical and biological data, including coagulation and fibrinolytic system-related parameters, were obtained every 6 months during follow-up. Occurrence of VTE was the primary outcome of the study. Results: We enrolled 56 patients (52±11 years, 64% men). Median follow-up time was 12 [IQR: 12, 33] months. During follow-up 11 VTE occurred, 91 % of them in the first six months. Baseline proteinuria and serum albumin were associated with VTE (p<0.001). As for the haemostatic parameters, antithrombin III (ATIII) activity, protein C activity, plasminogen activator inhibitor-1 (PAI-1) and tisular plasminogen activator (tPA) levels were associated with an increased risk of VTE (all p<0.05), while protein S activity and fibrinogen were not. At multivariable analysis only ATIII activity (Exp(B) 0.86, 95% CI 0.75 to 0.98; p = 0.027) and serum albumin (Exp(B) 0.062, 95% CI 0.01 to 0.37; p = 0.002) remained independently associated with VTE. Conclusion: In this prospective study the risk of VTE was higher in the first 6 months of follow-up. Among the haemostasis-related parameters, only ATIII deficiency emerged as VTE independent risk factor in adult patients with idiopathic membranous nephropathy and NS.