Association between dipeptidyl aminopeptidase IV activity and recurrence of Focal Segmental Glomerulosclerosis

• Grant number: 24/10040-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Bosco Pesquero
• Grantee: Isadora Gonçalves Almeida
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Focal and Segmental Glomerulosclerosis (FSGS) is the leading cause of kidney disease worldwide and is characterized by excessive loss of podocytes. In approximately 20% of cases, FSGS is secondary to other underlying diseases, while in 80% of cases it is idiopathic, known as primary FSGS. Although kidney transplantation is a treatment option, around 40% of patients experience recurrence of primary FSGS after the procedure. Since 1972, the presence of circulating factors responsible for this relapse has been suggested, but the exact mechanism and molecule responsible have not yet been fully elucidated, despite ongoing research efforts in this area. The main suggestions of circulating factors are strongly related to the immune system and inflammation mechanisms, such as the kallikrein-kinin system, especially bradykinin (BK), which is a peptide related to inflammatory processes, cell remodeling and increased permeability. In cases of FSGS, the metabolism of BK is of interest, especially through the action of the enzyme dipeptidyl aminopeptidase IV (DPP-IV), which may have its activity altered in nephrotic syndrome. The objectives include: 1) Evaluating the activity of DPP-IV, ACE and ACE2 in the plasma of individuals with pre-transplant idiopathic cortico-resistant FSGS; 2) Associating the enzymatic activity of DPP-IV, ACE and ACE2 with the occurrence or not of post-transplant idiopathic FSGS recurrence. Individuals diagnosed with idiopathic cortico-resistant FSGS at the Hospital do Rim who will subsequently undergo kidney transplant surgery will be invited to take part in this study. The activities of DPP-IV, ACE and ACE2 in plasma will be measured using enzyme kinetics assays.