Biomarkers of endothelial dysfunction in patients with primary focal segmental glomerulosclerosis

Abstract

Endothelial dysfunction occurs in nephrotic syndrome (NS) and may constitute a link between NS and vascular complications. Focal segmental glomerulosclerosis (FSGS) is a common cause of NS. This study aimed to assess endothelial markers at different stages of FSGS and define whether they were associated with thromboembolic complications and disease activity. Forty-four patients with nephrotic-range proteinuria and biopsy-proven primary FSGS were included in this study. Nine of them had concurrent thromboembolisms. Thirty-two sex- and age- matched healthy volunteers served as controls. Endothelial markers including circulating endothelial cells (CECs), soluble thrombomodulin (sTM), von Willebrand factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin were assessed at the commencement of the study in all participants and were repeated at 2, 6 and 12 months of follow-up in patients without thromboembolisms. Patients with FSGS during active stage showed significantly higher levels of CECs, sTM, vWf, sVCAM-1 and sE-selectin when compared with controls. Moreover, patients with thromboembolisms had higher CECs and vWf than those without thromboembolisms. In patients without thromboembolisms, endothelial markers except sE-selectin had inverse correlations with serum albumin and were positively related to cholesterol. Multiple analyses showed that cholesterol and serum albumin were independent predictors of CECs and sTM, and vWf and sVCAM-1, respectively. At follow-up, these markers systematically decreased as the disease went into remission, but the increase in vWf and sVCAM-1 persisted even in patients obtaining complete remission for nearly a year. In patients with no response, levels of endothelial markers exhibited no obvious change. Patients with FSGS had elevated markers of endothelial dysfunction, which were largely related to the activity of the disease. Meanwhile, levels of CECs and vWf were higher in patients concurrent with thromboembolisms.