|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||July 01, 2012|
|Effective date (End):||December 31, 2015|
|Field of knowledge:||Health Sciences - Medicine - Medical Clinics|
|Principal Investigator:||Maria Lucia Cardillo Corrêa Giannella|
|Grantee:||Maria Beatriz Camargo Monteiro Caillaud|
|Home Institution:||Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil|
Diabetic nephropathy (DN) is classically divided into five stages, with the following characteristics: 1) glomerular hyperfiltration, 2) normal urinary albumin excretion (UAE), 3) incipient DN with persistent microalbuminuria, 4) overt DN characterized by proteinuria and decreased glomerular filtration rate (GFR) and 5) end stage renal disease (ESRD). Several studies have shown, however, that UAE and the decline in renal function may not evolve in parallel and that GFR may decrease in the absence of abnormal UAE. In addition, recent evidence suggests that in patients with chronic kidney disease (CKD), the extent of renal dysfunction seems to correlate better with tubulointerstitial injury than with glomerulopathy. It is known that concentrations of oxidative stress markers are increased in diabetic patients. The thioredoxin (Trx) system is a major endogenous antioxidant system. TRX is able to interact with a large number of transcription factors and proteins such as Trx interacting protein (TXNIP). Recently, the involvement of TXNIP has been recognized in the pathogenesis of diabetes mellitus (DM) and its complications. Data indicate that this protein plays an important role in the progression of DN. Deficiency of thiamine, or B1 vitamin, has been reported in experimental models of diabetes concomitantly with an increase in its renal clearance. Thiamine transporter 1 (THTR-1), encoded by the SLC19A2 gene and Thiamine transporter 2 (THTR-2), encoded by the SLC19A3 gene are responsible for thiamine reabsorption in the proximal tubule after glomerular filtration. Studies have shown that increased urinary excretion of thiamine may be a risk predictor for an early decline in kidney function in diabetic patients. The objective of this study is to evaluate the role of the genes TXNIP, SLC19A2 and SLC19A3 in the pathogenesis of DN in patients with type 1 DM. To this end, messenger RNA (mRNA) will be extracted from the urinary sediment of diabetic patients to assess the expression of target genes, that will be associated with the clinical manifestations of ND, in four groups of patients: (1) normoalbuminuria and GFR> 60 mL /min (2) microalbuminuria and GFR <60 mL /min, (3) macroalbuminuria and GFR> 60 mL /min and (4) macroalbuminuria and GFR <60 mL/min. The study of activation or inactivation of intrarenal pathways potentially associated with progression of DN in humans is complicated by the need for renal biopsy. With the recent development of reliable techniques for extracting RNA from the urinary sediment and RT-qPCR, mRNA analysis of urinary sediment can become a tool in the evaluation of renal diseases, both in an attempt to identify biomarkers that can predict the evolution of renal function as well as for a better understanding of the pathogenesis of this complication.