BMC Seminar - Mechanisms of Kidney Injury in APRT Deficiency

BMC Seminar Thursday 30th of April at 12:00-13:00 in Askja, room N-132

Speaker: Hildur Rún Helgudóttir, PhD student under supervision of Þórarinn Guðjónsson, Faculty of Medicine, University of Iceland

Title: Mechanisms of Kidney Injury in APRT Deficiency

Abstract: Adenine phosphoribosyltransferase (APRT) deficiency is a rare genetic disorder that results in excessive generation and excretion of 2,8-dihydroxyadenine (DHA), leading to kidney stone disease and crystal nephropathy. This condition is associated with inflammation and fibrosis in the kidney, yet the mechanisms underlying DHA-induced cellular injury remain incompletely understood. In this project, I combined immunohistochemical analysis of human kidney tissue with in vitro epithelial cell models to characterize crystal localization, tissue injury, and molecular responses. In kidney tissue, DHA crystals were identified within tubular lumina, epithelial cells, and the interstitium, and were associated with inflammation and early fibrotic remodeling. In vitro, DHA exposure reduced epithelial cell viability, impaired migration, and disrupted barrier integrity, accompanied by cytoskeletal remodeling and activation of inflammatory and metabolic stress pathways. To better model the disease, I am now developing a CRISPR-based APRT knockout cell system to replicate the underlying metabolic defect and investigate endogenous DHA-related stress. Together, these findings link crystal deposition to epithelial dysfunction and provide a framework for understanding DHA-induced kidney injury and identifying potential therapeutic targets.

Bio: Hildur Run Helgudottir is a PhD student in Biomedical Sciences at Þórarinn Guðjónsson's lab at Univeristy of Iceland. She completed her BSc in Biology in 2019 and her MSc in Biomedical Sciences in 2021, both at the University of Iceland. She started her PhD in 2021.