Single-cell RNA sequencing identifies a unique population of macrophages in the Aristolochic acid I (AAI)-induced AKI-to-CKD transition murine model

Acute Kidney Injury (AKI) often progresses to Chronic Kidney Disease (CKD), resulting in significant morbidity and mortality. The transition from AKI to CKD is driven by complex cellular mechanisms that are not yet fully understood. In this study, we used an Aristolochic Acid I (AAI)-induced murine model to investigate these mechanisms, performing single-cell RNA sequencing (scRNA-seq) to comprehensively profile kidney immune cells during the AKI to CKD transition. Our analysis revealed significant changes in immune cell populations, particularly macrophages and T lymphocytes. We identified a novel subpopulation of macrophages characterized by the expression of Ctsk, Mmp9, and Acp5, which emerged during the CKD phase. These macrophages were found to interact with T cells, injured proximal tubules, and fibroblasts, suggesting their involvement in chronic inflammation and fibrosis. Targeting this specific macrophage subpopulation may represent a potential therapeutic approach to prevent CKD progression. Additionally, T lymphocytes underwent a transition from effector to exhausted phenotypes, indicating chronic immune activation and sustained inflammation in CKD. Our findings provide new insights into the immune landscape of kidney injury and highlight potential targets for therapeutic intervention in preventing the progression from AKI to CKD.