Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease

Abstract

Abstract. Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r= 0.242, P= 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P= 0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis

“…Quantification is relative to 270 mosmol/kg (mean ± SEM, *P < 0.05, t test, n = 5, linearly dependent on NaCl concentration, P < 0.0001). The NFAT5 mRNA returns to the basal level when NaCl is levels of VWF (26,27). Consistently, there is significant zero-order correlation of plasma glucose and eGFR with level of vWF (Table S3).…”

Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease

“…33 Further studies have suggested that, in addition to reflecting glomerular injury, albumin secretion is also pathogenic, leading to proinflammatory and profibrotic events within the proximal tubule. 34–35 While the mechanisms by which albuminuria is associated with cardiovascular events are not fully understood, it has been postulated that albuminuria may reflect systemic endothelial dysfunction 36–37 that alters inflammatory and thrombotic cascades 38–39 and contributes to atherothrombotic events, including stroke.…”

Simvastatin Increases ADAMTS13 Expression in Podocytes

“…Our previous study has suggested that ADAMTS13 activity was decreased and TNF-α level increased in patients with chronic kidney [9]. Recently, an in vivo study demonstrated that patients with alcoholic hepatitis had low ADAMTS13 activity but elevated levels of inflammatory cytokines in the plasma [10].…”