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The aim of this study is to investigate whether Syndecan-1 (SDC-1), an indicator of endothelial glycocalyx injury, would increase the risk of hypercoagulable state and thrombosis in patients with nephrotic syndrome (NS). The prospective study was conducted among patients undergoing renal biopsy in the Department of Nephrology in our hospital from May to September 2018. We enrolled in patients with NS as the experimental group and patients with normal serum creatinine and proteinuria less than 1 g as the control group. Patients’ characteristics including age, sex, laboratory test results and blood samples were collected for each patient. The blood samples were taken before the renal biopsy. The samples were immediately processed and frozen at −80°C for later measurement of Syndecan-1. One hundred and thirty-six patients were enrolled in the study. Patients with NS and hypercoagulability had a higher level of SDC-1 compared with control group. Patients with membranous nephropathy occupied the highest SDC-1 level ( P = 0.012). Logistic regression showed that highly increased level of SDC-1 (>53.18 ng/ml) was an independent predicator for predicting hypercoagulable state. The elevated level of SDC-1 indicated that endothelial injury, combined with its role of accelerating hypercoagulable state, might be considered of vital importance in the pathophysiological progress of thrombosis formation in patients with NS.