Investigation of the vascular inflammatory state in models of acute kidney injury: effect of P-cresyl sulfate on purinergic signaling

• Grant number: 24/03888-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Victor da Silva Jacyntho
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 24/07191-0 - Investigation of the vascular inflammatory state in kidney injury models: contribution of purinergic signaling, AP.R

Abstract

Acute kidney injury (AKI) is a sudden reduction or loss of kidney function that persists for up to 3 months and can be caused by various stimuli, such as ischemia and reperfusion injury (IR) and/or accumulation of uremic toxins (UT) such as p-cresyl sulfate (PCS). IR injury is the main cause of AKI as it is associated with necrosis of renal tubular endothelial cells, in situ and systemic inflammation, and fibrosis. In the liver, p-cresol (solute resulting from bacterial fermentation in the intestine) is sulfated and transformed into PCS, which under normal conditions is excreted in the urine or feces. In dialysis patients, serum PCS concentration is 17 times higher than in healthy individuals. The accumulation of PCS impacts several organs and systems, including the vasculature, as it acts pro-oxidant on smooth muscle cells. Purinergic signaling plays an important role in control and remodeling, as it can influence platelet activation and vasomotor response. Considering the above, this study hypothesizes that vessels distant from the site of renal ischemia, such as the aorta, are altered by the inflammatory state of AKI, triggered by both IR and TU or by the combination IR+TU, and such changes are due, at least in part, to an imbalance of vascular purinergic components.