Avaliação da função renal e sua associação com FVW, ADAMTS13 e dímero D em pacientes diabéticos tipo 1

Abstract

Diabetic nephropathy is the most important cause of end stage renal disease in adults and an idependent risk factor for cardiovascular disease. Endothelial dysfunction along with the development of a hypercoagulability state have been associated with the development of diabetic vascular complications. Thus, this study aimed to evaluate the renal function of type 1 diabetic patients using different methodologies and their association with plasma levels of biomarkers of endothelial dysfunction, VWF and ADAMTS13, and the biomarker of hypercoagulability, D-Dimer. Diabetic patients were classified into three groups according to glomerular filtration rate (GFR): GFR 90mL/min/1,73m2, n=52; GFR 60 e <90mL/min/1,73m2, n=29; GFR <60mL/min/1,73m2, n=28; and also according to albuminuria: <30mg/g, n=53; 30 e <300mg/g, n=26; 300mg/g, n=30. Plasma levels of VWF, ADAMTS13, D-Dimer and cystatin C were determined by ELISA, ADAMTS13 activity was evaluated by FRET, and GFR was estimated using equations based on creatinine or cystatin C. GFR estimated by creatinine-based or cystatin-based equations presented a good correlation with different levels of albuminuria. However, equations based on cystatin C presented a slightly higher accuracy for detecting the presence of severe increased albuminuria. Increased plasma levels of VWF, ADAMTS13 and D-Dimer, increased ADAMTS13 activity, and reduced ADAMTS13Activity/ADAMTS13Ag ratio were significantly associated with the decline of GFR and increased albuminuria, indicating an association between endothelial dysfunction and hypercoagulability with nephropathy in type 1 diabetes mellitus (DM1). Only albuminuria and cystatin C were independently associated with increased levels of D-Dimer. Therefore, cystatin C was the biomarker of renal function that presented a greater association with severe increased albuminuria and with increased levels of D-Dimer, which demonstrates the great potential of this biomarker to simultaneously assess renal function and the risk of cardiovascular disease in DM1. As all the methodologies to evaluate renal function have advantages and limitations, ideally, all of them should be used complementarily. Moreover, it is very important to search for new biomarkers of renal function that enable early detection of renal disease, its progression and its complications. As increased plasma levels of VWF and D-Dimer, and reduced ADAMTS13Activity/ADAMTS13Ag ratio are associated with diabetic nephropathy, these biomarkers of endothelial dysfunction and hypercoagulability are very promising to be used in monitoring renal disease in DM1.