Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury

Abstract

Chronic Kidney Disease (CKD) involves the participation of a series of inflammatory events that culminate in fibrosis of the renal parenchyma. The reasons why these processes, which involve the activation of phenomena related to adaptive immunity, are triggered in the absence of microbial antigens or other foreign proteins are uncertain. With the new knowledge about the innate immunity, accumulated since the discovery of toll-like receptors (TLRs) in the mid-1980s and expanded in recent years with the description of intracellular receptors and inflamasomes, and of their interaction with the NF-kB system, these questions begin to be answered. In CKD, analogously to what is believed to occur in gout and in pneumoconiosis - inflammatory responses evoked by foreign bodies - it is possible that activation of innate immunity represents the link between nonspecific events, such as stretching of the glomerular wall, and inflammatory processes leading to renal fibrosis and glomerulosclerosis. The hypothesis on which the present research projects are centered is that at least some forms of CKD result of, and/or are perpetuated by, the activation of innate immunity by factors such as mechanical injury to the glomeruli or the exposure of cells to chemical aggression such as high levels of glucose or proteins. These projects will also clarify previous observations from our laboratories and will afford the opportunity to investigate new therapies designed to contain the inflammatory events that conduce to CKD and its progression. (AU)