Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury.

This article focuses on the immune cell dynamics and cellular senescence in rhabdomyolysis-induced acute kidney injury (RM-AKI) using single-cell RNA sequencing in a murine model. It identifies a novel transitional macrophage subpopulation (Cluster 8) characterized by a cellular senescence gene signature that acts as a reprogramming node between major histocompatibility complex class II high (MHCII^high) macrophages in healthy kidneys and MHCII^low macrophages in RM-AKI. The study also demonstrates that tubular epithelial cells (TECs) exhibit a distinct senescence signature during AKI. Treatment with senolytics—dasatinib and quercetin (DQ)—administered before and after injury prevented the macrophage phenotypic switch, reduced kidney injury markers, and improved renal function, suggesting that senolytics may exert nephroprotective effects through modulation of immune cell senescence in early RM-AKI.