IDENTIFICATION OF EPIGENETIC FACTORS RELATED TO ACUTE KIDNEY INJURY (AKI) AND PROGRESSION TO CHRONIC KIDNEY DISEASE (CKD)

Acute Kidney injury (AKI) remains a relevant problem in critically ill patients with high risk of mortality and progression to chronic kidney disease (CKD) and end stage renal disease (ESRD). The lack of understanding the pathophysiology of AKI and AKI-to-CKD transition has led to the failure of all treatments proposed for AKI and the persistence of negative long-term outcomes. A more personalized approach, based on the recognition of several AKI phenotyes, is critical to improve clinical outcomes. In this project, we will investigate the molecular mechanisms involved in the AKI-to-CKD transition, testing whether the epigenetic changes occurring during an AKI episode might significantly contribute to the progression to CKD/ESRD. To test this hypothesis, we will collect clinical data and biological samples from patients admitted to both intensive care units (ICUs) and medical/surgical wards who develop AKI during hospitalization; we will follow up them and collect clinical data and biological samples up to 12 months after hospitalization in order to assess the progression to CKD/ESRD during the follow up period. We will use an innovative approach, such as high-throughput techniques, to analyze the epigenetic changes occurred during the study period to characterize a specific phenotype of AKI progressors. In addition, we will test several AKI biomarkers that may be applied for risk prediction of AKI-to-CKD transition in combination with clinical and laboratory data. Finally, the isolation and characterization of extracellular vescicles (EVs) will be performed to test their correlation with the risk of AKI-to-CKD progression. This integrated approach might lead to the identification of different AKI phenotypes with different risk for progression to CKD, and new potential therapeutic targets to prevent AKI and the progression to CKD.