Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus

Abstract

We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: ≥90 and <130mL/min/1,73m2, n=52 (control group), ≥60 and <90mL/min/1,73m2, n=29 (mild renal dysfunction group), <60mL/min/1,73m2, n=28 (severe renal dysfunction group); and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001) and severe (P<0.001) renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029) and severe (P=0.002) renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006). No significant differences were observed among the groups regarding von Willebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013) and severe (P=0.015) renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006) and severe (P<0.001) renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019). Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes, suggesting that endothelial dysfunction and hypercoagulability are associated with nephropathy in type 1 diabetes.