Impact of Necroptosis on the Outcome of Delayed Graft Function After Renal Transplantation

• Grant number: 23/17940-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Érika Bevilaqua Rangel
• Grantee: Rafaela Francisquetti Barnes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Organ transplantation is an important renal replacement therapy for significant pathologies in the current spectrum of global health, such as Chronic Kidney Disease (CKD). This disease affects a considerable portion of patients across various ages, genders, and ethnicities. The generally asymptomatic and prolonged course of CKD can lead to systemic involvement and significant kidney injuries, which, like other pathologies, may require transplant-mediated treatment or dialytic treatment. Although the wait for organ transplantation is often less than ideal for the proper management and recovery of patients, post-transplantation, various outcomes can be observed that directly impact the success or failure of the procedure, influencing the survival of both patients and the renal graft. Delayed Graft Function (DGF), a late graft function, is an outcome observed in a considerable range of renal transplant procedures. This scenario can be associated with various external factors, such as cold ischemia time and ischemia-reperfusion injury, as well as various molecular signaling pathways, such as cell death by necroptosis. Understanding the impact of necroptosis on the occurrence of DGF after renal transplantation allows for the identification of potential therapeutic targets. For this purpose, histological analysis of biopsies from deceased donors diagnosed with acute tubular necrosis with DGF and without DGF will be performed, along with the analysis of proteins specifically involved in necroptosis (p-MLKL, p-RIPK1, and p-RIPK3) through immunohistochemistry assays. We will also analyze data from deceased donors and recipients to identify health parameters and transplant conditions, as well as the evolution of patients after the procedure. Among the expected results, scenarios and outcomes that can be used to identify the causes and associations between DGF and necroptosis after renal transplantation will be highlighted, as well as the relationship between late graft function and necroptosis, and therefore, biomarkers of this process, as previously indicated in scientific investigations.