title: 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.
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Caroline Pereira
authors.initials: CP
authors.lastname: Domingueti
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luci Maria S
authors.initials: LM
authors.lastname: Dusse
authors.affiliation: Department of Medical Clinic, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rodrigo Bastos
authors.initials: RB
authors.lastname: Fóscolo
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Education and Research of Santa Casa of Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Janice Sepúlveda
authors.initials: JS
authors.lastname: Reis
authors.affiliation: Laboratory of Hemostasis, Hemocenter of Campinas, University of Campinas, São Paulo, Brazil.
authors.forename: Joyce Maria
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
authors.affiliation: Laboratory of Hemostasis, Hemocenter of Campinas, University of Campinas, São Paulo, Brazil.
authors.forename: Fernanda Loureiro de Andrade
authors.initials: FL
authors.lastname: Orsi
authors.affiliation: Laboratory of Hemostasis, Hemocenter of Campinas, University of Campinas, São Paulo, Brazil.
authors.forename: Bruna de Moraes
authors.initials: Bde M
authors.lastname: Mazetto
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Maria das Graças
authors.initials: Md
authors.lastname: Carvalho
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Karina Braga
authors.initials: KB
authors.lastname: Gomes
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human