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The role of innate immunity in CKD following treatment with a temporary overload of the adenine diet

Grant number: 15/20255-9
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): January 01, 2016
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Roberto Zatz
Grantee:Gizely Cristina da Silva Moreira
Supervisor abroad: Benjamin D. Humphreys
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Washington, United States  
Associated to the scholarship:13/26947-4 - The role of innate immunity in CKD following treatment with a temporary overload of the adenine diet, BP.MS

Abstract

The excess dietary adenine (ADE) intratubular promotes precipitation of crystals, leading to a progressive installation of interstitial nephritis and renal function loss. Recent observations indicate that the overhead of ADE in mice in which genes for TLR-2, -4, MyD88, ASC or caspase-1 have been inactivated causes less damage to the kidney compared to administered to wild type mice, suggesting the existence of a pathogenic role for activation of TLRs and formation of inflamassomas in this model. In a recent study, the overhead of adenine in the diet led to deposition of numerous crystals in renal tissue, mostly inside of foreign body granuloma, accompanied by severe tubulointerstitial proliferative activity. A part of the crystals appeared surrounded by a layer of cells apparently derived from the tubular epithelium, which appeared to segregate and precipitate in some cases, to drive them to interstitium. These changes were associated with a large expansion of the interstitial area with collagen deposition, and glomerular hypertrophy. These findings are consistent with the concept that the NF-kB system is activated by intratubular crystal precipitation and contributes, along with other mechanisms related to innate immunity, to begin intense inflammatory response associated with this model. It is widely known the progressive nature of chronic kidney disease (CKD): once started, the process tends to progress even after ceased the initial insult. The aim of this study is to study the activation of innate immunity and inflammatory phenomena associated with nephropathy caused by an overload of dietary adenine and investigate what promotes the perpetuation of the inflammatory process after termination of the initial insult.