A glimpse of the glomerular milieu: from endothelial cell to thrombotic disease in nephrotic syndrome

Patients with nephrotic syndrome (NS) carry a high risk of venous thromboembolism (VTE) due to the abnormalities in coagulation and fibrinolysis. Although massive urine protein loss is considered to trigger the cascade of hypercoagulation, the exact nature of VTE in NS patients still remains obscure, especially in some cases when VTE occurs far before the presence of nephrotic proteinuria. Recent findings illustrate that loss of local glomerular homeostasis, like disturbance of cytokine profiles in endothelial cells or aberrant cellular crosstalks in glomerulus, is sufficient to initiate the development of thrombotic disease in glomerulonephropathy. Emerging data have highlighted the glomerular endothelial cell as a key regulator of local homeostasis, which might mediate the haemostatic derangement in the beginning of glomerular disease by expression of numerous prothrombotic factors and result in the subsequent predilection of VTE in NS. As the glomerulus-derived circulating factors are all collected and flushed into the renal vein directly, it is reasonable to suggest that increased release of glomerulus-derived thrombotic regulators, particularly from endothelial cells, may play a significant role in the highest proclivity for the renal vein as the site of thrombosis in NS. In this review, we thus discuss the current understandings of thromboembolism in NS with focus on how the glomerular endothelial cell involves in the pathogenesis of VTE, which may help to increase our understandings in the anti-thrombotic therapy for patients with NS.