Epigenetic memories induced by hypoxia in AKI-to-CKD transition

Chronic kidney disease (CKD) is a global health burden associated with increasing mortality rates. Aging populations and declining fertility rates exacerbate this issue, particularly in countries such as Japan. Acute kidney injury (AKI) was previously considered temporary and reversible condition. However, in recent years, multiple studies on kidney diseases have shown that AKI survivors are at an increased risk of developing CKD. During the AKI-to-CKD transition, a subset of AKI-induced epigenetic alterations persists in cells, potentially driving the progression of tubulointerstitial fibrosis. Therefore, targeting epigenetic mechanisms may represent a promising therapeutic approach for preventing AKI-to-CKD transition. Among the epigenetic mechnisms involved, "hypoxic memory" plays a crucial role in this transition by inducing persistent epigenetic changes. Hypoxic memory induces DNA methylation, histone modification, changes in chromatin conformation, and long non-codingRNA (lncRNA) expression. Herein, we review the latest evidence on epigenetic memory in the AKI-to-CKD transition, identifying that the detailed mechanisms of epigenetic memory and temporal specificity are crucial for developing effective treatments.