A treatment using a component of innate immunity inhibitor on adriamycin nephropathy

Abstract

Chronic Kidney Disease (CKD) involves the participation of the several inflammatory events that end in fibrosis of renal interstitial even if the process has started only in the glomeruli. One of the biggest challenges of the nephrology is to stop the progression of nephropathy. In the clinical context, proteinuria correlates with progression of kidney diseases, in particular glomerular diseases. One of the main hypotheses proposed to explain this correlation between glomerular injury and interstitial inflammation is that the proteins passing through the defective glomerular barrier and gain tubular lumen exert a toxic effect on the cells of the proximal tubule, synthesising inflammatory mediators such as cytokines and chemokines. However, the mechanisms by which pro-inflammatory effect occurs after excess of the proteins exposure by tubular cells are not clear. Considering the knowledge over the past 20 years, it is conceivable that in consequence of the intense resorptive activity of the proximal epithelial cells, the high concentrations of proteins ends by activating some innate immunity pathways by lysosomes rupture, organelle essential to proteins hydrolysis. The innate immunity activation can be to influence the progression of nephropathy, it is conceivable that chronic inhibition of the innate immunity components promote renoprotective effects in CKD, opening a new therapeutic approach. In this study, it was hypothesized that inhibition of the NFkB pathway or NLRP3 inflammasome activity results in protection against the progression of proteinuric nephropathy in a known model of acute glomerular barrier dysfunction by adriamycin administration. (AU)