Extracellular Vesicles as Mediators of Immunological Changes in the Progression of Acute Kidney Injury to Chronic Kidney Disease

• Grant number: 25/28438-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2026
• End date: January 31, 2030
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Beatriz Favero Bedin
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• Associated research grant: 24/02928-5 - Cardiac shifting from structural changes to electrical alterations during acute kidney injury to chronic kidney disease transition., AP.TEM

Abstract

Acute kidney injury (AKI) is characterized by the sudden loss of kidney function for up to seven days and, when there is no complete recovery, it can evolve into acute kidney disease (AKD) or even progress to chronic kidney disease (CKD). Acute tubular necrosis (ATN) is one of the main causes of AKI and is a strong precursor to CKD. Among experimental models, adenine overload is widely used because it generates dihydroxydiadenine (DHA), a poorly soluble metabolite that precipitates in the form of crystals in the renal tubules, generating constant episodes of ATN. In this context, extracellular vesicles (EVs) have emerged as important intercellular signaling molecules, acting in physiological and pathological processes through the transport of bioactive biomolecules between cells. Evidence indicates that EVs participate in immune activation, modulation of cell damage, cell death mechanisms, and oxidative stress pathways during AKI. However, it is still poorly understood how systemic endothelial veins (cVVs) and those produced locally in the tubular epithelium (mcVVs) contribute to the mechanisms that regulate the transition from acute renal failure (ARF) to chronic kidney disease (CKD). Our hypothesis is that cVEs and mcVEs modulate important cellular responses that determine the progression of kidney damage. Thus, this project aims to investigate the role of systemic and local EVs in kidney injury and the immune response during AKI and its evolution to CKD. In vivo experiments will be performed to characterize the temporal nature of the injury, the immunological profile, and the isolation and characterization of circulating and local EVs, and in vitro experiments to evaluate the effects of cVEs and mcVEs on proximal tubular epithelial cells (PTECs), addressing mechanisms of cell death (MTT and Annexin-PI), cell cycle, production of reactive oxygen species (MitoSOX and H2DCF-DA), and inflammatory signaling profiles (multiplex). (AU)