Postmortem study of factors associated with renal senescence and ultrastructural changes in the glomerular barrier in humans: effects of air pollution and/or Covid 19

• Grant number: 24/13832-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: January 31, 2027
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Mariana Matera Veras
• Grantee: Dunia Waked
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/06944-0 - The autopsy as a tool for the study of the disease process and health inequalities in urban areas, AP.TEM

Abstract

Chronic Kidney Disease (CKD) is recognized as an increasingly significant public health issue, resulting in high morbidity and mortality rates globally. CKD is closely related to cardiovascular diseases and diabetes, and atmospheric pollution has been evidenced as an exacerbating factor for various health conditions. Inhalable fine particles can reach the pulmonary alveoli and subsequently enter the systemic circulation, causing inflammation and affecting multiple organs. Exposure to pollutants leads to inflammation, oxidative stress, DNA damage, and increased fibrosis deposition in renal tissue, resulting in epithelial cell damage and impaired glomerular filtration barrier efficiency. Cellular senescence is characterized by irreversible cessation of cell proliferation, functioning as a defense mechanism to prevent the uncontrolled proliferation of cells with compromised function. This process can result from multiple cell divisions. The increase in senescent cells in renal tissue is associated with glomerular damage, loss of podocytes, and consequently, diminished renal function. The COVID-19 pandemic has added a new layer of complexity to this situation. SARS-CoV-2 infection can cause acute kidney injury and exacerbate preexisting renal conditions. COVID-19 patients often present with an exacerbated inflammatory response, which may accelerate cellular senescence and worsen CKD. Additionally, Long COVID, a condition where symptoms persist for weeks or months after the acute phase of the disease, may also contribute to long-term renal function deterioration. The aim of this study is to evaluate the interaction between atmospheric pollution and COVID-19 infection with the potential acceleration of cellular senescence and renal structural damage. To achieve this, renal tissues collected from autopsies through the Death Verification Service (DVS) will be assessed. After collection, the tissues will be sent for morphological analysis via histology, and a portion will be frozen for molecular analysis of senescence markers and renal damage. As a measure of exposure to pollution, surface photographs of the lungs will be taken, where the fraction of anthracosis will be quantified for subsequent correlation with other study findings.