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Effect of treatment with an innate immunity component inhibitor in adriamycin nephropathy

Grant number: 16/08525-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2016
Effective date (End): April 30, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Clarice Kazue Fujihara
Grantee:Leonardo Lódola Tavares
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury, AP.TEM

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 will check the hypothesis that neutralizing an important component of innate immunity (IL -1 ), by an antagonist of the IL- 1 receptor (Anakinra), results in protection against progression of proteinuric nephropathies in a known model of acute dysfunction of glomerular barrier - adriamycin administration. (AU)