The role of innate immunity in chronic kidney disease stablished after recovery nephropathy induced by temporary inhibition of nitric oxide associated with a saline overload

Abstract

It is well known that Chronic Kidney Disease affects approximately 10% of the population around the world. Unfortunately, the understanding of the chronic renal injury mechanisms and how to treat them, are still distant. However, it is known that mechanical factors such as, hypertension and glomerular hypertrophy, and a series of inflammatory events in the loss of renal function are participating in this process. In 1992, our research team published a new model of hypertension by chronic administration of a Nitric Oxide inhibitor, N-L-Nitroarginina Metilester (L-NAME). Later on, we showed that a high salt diet associated with this treatment led to anaggravated hypertension, a massive proteinuria, and the development of glomerular and interstitial lesions. It was also noticed a regression in the proteinuria and blood pressure levels, and the most renal injures, 30 days after ceasing the treatment. However, the normal levels were never completely achieved. After six months, proteinuria and blood pressure levels were increased again, and a process of glomerulosclerose and interstitial fibroses had been stablished. Based on this information, we suggest that these abnormalities are result of a persistent activation of one or more components of innate immunity in glomerular and/or tubular cells, leading to the development of inflammatoryevents that cause additional cellular injury, perpetuating the process. As experimental strategy, rats with short-term treatment with L-NAME and saline overload will be monitored over six months, with measurement at certain times, of a series of structural and functional parameters. Inflammatory elements and components of innate immunity present in this process will be exanimated. Therefore, it will investigate infiltration by macrophages, nuclear translocation of NF-kB system, gene expression and kidneycontent of TLR4, IL-1, NLRP3, and caspase-1. We will also analyze renal tissue by PCR-array to identify others compounds that may be involved in renal injures mechanisms associated with this experimental model. (AU)