Role of kinin receptor B1 in the recurrence of primary focal segmental glomerulosclerosis

• Grant number: 18/07712-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2018
• End date: December 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: João Bosco Pesquero
• Grantee: Fernanda Maria Serafim Casimiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Focal Segmental Glomerulosclerosis (FSGS) is the leading cause of kidney disease worldwide. It is characterized by excessive loss of podocytes. Clinically, loss of podocytes and hence their filtration function results in nephrotic syndrome (NS), consisting of proteinuria, hypoalbuminemia, hypercholesterolemia and peripheral edema, clinical features typical of FSGS, which is the most common cause of NS.In 20% of cases, FSGS is a result of other underlying diseases, called secondary FSGS. The majority of cases of FSGS are of idiopathic cause (80%) and are called primary FSGS. However, although transplantation is a potential treatment, about 40% of patients have recurrence of primary FSGS after transplantation.Due to this fact, in 1972 the presence of circulating factors responsible for relapse of primary FSGS after transplantation was suggested for the first time. Since then researchers have sought to understand and characterize the supposed circulating factor. In fact, several molecules have been chosen candidates, however, the molecule itself and the exact mechanism have not yet been discovered and are not very well elucidated.The work in question hypothesizes that the circulating factors described so far have a common activation pathway, such as the activation of NF-kB, which will induce expression of kinin receptors B1, which will be responsible for promoting vasodilation and increased permeability of the renal tissue, leading to the characteristic symptoms of FSGS, such as proteinuria, hypoalbuminemia and edema.To try to prove this hypothesis, we will standardize a FSGS model in rats, using systemic plasma infusion of relapsed patients of primary FSGS after renal transplantation. Next, we will validate and characterize the model through biochemical, histological and molecular analyzes to verify renal function over time. Concomitantly, we will analyze the profile of kinin receptor B1 expression and its relation to the histopathological and physico-clinical findings associated with primary FSGS. (AU)