Driving role of macrophages in transition from acute kidney injury to chronic kidney disease

Abstract

Acute kidney injury (AKI), characterized by acute renal dysfunction, is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease (CKD). Regardless of the initial insults, the progression of CKD after AKI involves multiple types of cells, including renal resident cells and immune cells such as macrophages. Recently, the involvements of macrophages in AKI-to-CKD transition have garnered significant attention. Furthermore, substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis. In this review, we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization, and transdifferentiation in the development of AKI-to-CKD transition. In addition, the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.

Figure 1

Macrophages in AKI-to-CKD progression. Macrophages derived from bone marrow are recruited into the injured kidney and promote AKI-to-CKD by directly and indirectly Interacting with intrinsic kidney cells and via the process of MMT. AKI: Acute kidney injury; BRP: Breast regression protein; CKD: Chronic kidney disease; DAMPs: Damage-associated molecular patterns; MMT: Macrophage-myofibroblast transition; ECM: Extracellular matrix; MMP: Matrix metalloproteinase; M1: Macrophage 1 phenotype; M2: Macrophage 2 phenotype; Mø: Resident macrophage; TGF-β: Transforming growth factor-β.