Analysis of alternative events involved in the formation of renal fibrosis in vitamin D deficient rats submitted to nephrectomy 5/6

Abstract

In most countries, the incidence and prevalence of chronic kidney disease (CKD) has been increasing over the years. Although there has been a significant improvement in the management of CKD, the disease is still progressive, requiring the application of new protective strategies. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including transforming growth factor-²1 (TGF-²1). The mechanisms of renal disease progression and the integration between related molecular pathways remain unknown. It has been shown that the mortality of patients with CKD is directly related to renal function and is associated with traditional risks such as cardiovascular and infections. Increasing evidence shows that vitamin D status may be a non-traditional risk factor for CKD progression. In view of the essential role of vitamin D in renal physiology and mineral homeostasis, we propose to study its effects in an experimental model of CKD already established (nephrectomy 5/6) and analyze alternative pathways involved in the formation of renal fibrosis, including epidermal growth fator receptor (EGFr), in addition to inflammatory pathways and endothelial dysfunction. Wistar rats deficient in vitamin D will undergo 5/6 nephrectomy (Nx) and than we will allocate them into four groups for receiving Losartan, Erlotinib (EGFr inhibitor), Losartan + Erlotinib or no treatment. Animals will be euthanized 60 days after Nx surgery in order to evaluate functional and biochemical parameters. We will collect renal tissue for histomorphological evaluation and for immunohistochemistry and protein expression studies related to pathways of fibrosis formation, inflammation and endothelial dysfunction. (AU)