Acute Kidney Injury-to-Chronic Kidney Disease Transition-Associated Macrophage Subtypes: Biological Functions and Intercellular Crosstalk

As a core organ responsible for metabolism and homeostatic regulation, the kidney performs physiological functions that encompass material excretion, fluid balance, electrolyte regulation, and endocrine control; and serves as a critical hub for maintaining the coordinated functioning of multiple organ systems. Kidney injury not only leads to disturbances in these core physiological functions but also generates systemic complications such as cardiovascular disease, hypertension, and diabetes mellitus through an “injury–inflammation–metabolic disorder” cascade. Epidemiologic studies and clinical statistics have revealed that acute kidney injury (AKI) may progress to chronic kidney disease (CKD) because of maladaptive repair, impaired regeneration, and other factors. During this process, macrophages—particularly certain functionally specialized macrophage subtypes—engage in complex intercellular communication with neighboring cells that include renal tubular epithelial cells, endothelial cells, fibroblasts, and platelets, thereby forming pathological signaling networks that collectively drive persistent inflammation and the progression of renal fibrosis. Macrophages thus play complex and dynamic dual regulatory roles throughout the initiation, progression, and repair of kidney injury, and their functional polarization and phenotypic transformation directly influence the pathological progression of kidney diseases. We herein aimed to elucidate the roles of AKI-to-CKD transition-associated macrophages, especially the subtypes with specialized functions in kidney diseases and to systematically review current research progress, thus to provide a reference for advancing basic research and clinical diagnostic and therapeutic strategies for kidney diseases.