Cilastina en la prevención y tratamiento del fracaso renal agudo parenquimatoso de origen endotóxico.Sepsis y rabdomiólisis

Resumo

Parenchymal acute renal failure (ARF) is defined as a clinical entity secondary to multiple causes in which an abrupt deterioration of renal functions alters homeostasis and the composition of the internal environment. Sepsis and rhabdomyolysis are two complex syndromes that causes endotoxic parenchymal ARF due to the presence of lipopolysaccharide (LPS) and myoglobin respectively, which act as endotoxins. Both produce damage by inducing renal vasoconstriction, inflammation, oxidative stress, cell death and tubular obstruction. There is currently no specific drug for the prevention or treatment of ARF in the context of sepsis and rhabdomyolysis so, the search for novel protective strategies with Clinical application is a priority task. In previous studies by our group that cilastatin, a competitive inhibitor of the renal dehydropeptidase-I (DHP-I) enzyme located in the cholesterol rafts (CR) of proximal tubule epithelial cells, protects renal tubule from damage. In models of ARF induced by different compounds commonly used in the clinic with nephrotoxic properties, the protective effect of cilastatin was due in part to interference with the CR, which either reduced or halted key steps in the auto- and paracrine signaling of the extrinsic pathway of apoptosis...