The Impact of Versatile Macrophage Functions on Acute Kidney Injury and Its Outcomes

Acute kidney injury (AKI) is a common and devastating clinical condition with a high morbidity and mortality rate and is associated with a rapid decline of kidney function mostly resulting from the injury of proximal tubules. AKI is typically accompanied by inflammation and immune activation and involves macrophages (Mϕ) from the beginning: The inflamed kidney recruits “classically” activated (M1) Mϕ, which are initially poised to destroy potential pathogens, exacerbating inflammation. Of note, they soon turn into “alternatively” activated (M2) Mϕ and promote immunosuppression and tissue regeneration. Based on their roles in kidney recovery, there is a growing interest to use M2 Mϕ and Mϕ-modulating agents therapeutically against AKI. However, it is pertinent to note that the clinical translation of Mϕ-based therapies needs to be critically reviewed and questioned since Mϕ are functionally plastic with versatile roles in AKI and some Mϕ functions are detrimental to the kidney during AKI. In this review, we discuss the current state of knowledge on the biology of different Mϕ subtypes during AKI and, especially, on their role in AKI and assess the impact of versatile Mϕ functions on AKI based on the findings from translational AKI studies.