Jose Reyes
Associate Professor
Title: Initial Stages of diabetic nephropathy: The beginning of a catastrophe
Biography
Biography: Jose Reyes
Abstract
Diabetes is a public health problem worldwide distributed, affecting over 300 million patients. Diabetic nephropathy represents a major complication leading to end stage renal disease (ESRD). Treatment for this condition is dialysis, since frequently these patients are not candidates for transplantation. This evolution is fully recognized, however, initial mechanisms of renal damage in diabetes are not fully established. It is recognized that hyperglycemia provokes oxidative stress, which derives in damage to intercellular tight junctions. Aim of this study is to analyze the functional damage induced by oxidative stress on several segments of the nephron (functional unit of the kidney) and the participation of the tight intercellular junctions (TJs) that are expressed in those segments. We found an extensive oxidative stress at glomeruli (filtration units) and at proximal tubules (site of reabsorption of glucose and sodium). Damage of TJ junctions at endothelial cells explaining proteinuria and at epithelial proximal cells, explaining glucosuria and augmented natriuresis, were observed. Oxidative stress was reduced by administration of All-Trans Retinoic Acid (ATRA), vitamin A active form. As a consequence of reduced oxidative stress by ATRA, proteinuria and abnormalities in sodium renal handling were ameliorated, even in the presence of persistent hyperglycemia. This ATRA beneficial effect was accompanied by improvement of the TJs proteins damage. These data provide evidence of renal TJs as potential therapeutic targets on the evolution and progression of diabetic nephropathy