Neutrophil-mediated acute kidney injury and its progression to chronicity

Abstract

Summary Neutrophils are primary effectors of the innate immune system, modulating tissue homeostasis and disease through phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). While neutrophil infiltration is a defining hallmark of acute kidney injury (AKI), its complex role in orchestrating the transition from acute damage to chronic fibrosis is not yet fully understood. This review provides a comprehensive synthesis of the spatiotemporal mechanisms underlying neutrophil involvement in renal pathology, incorporating recruitment cascades, phenotypic activation, and pathogenic implications of NETosis. We specifically deconstruct the spatiotemporal mechanisms and heterogeneous functional subsets by which neutrophils orchestrate the AKI-to-chronic kidney disease (CKD) transition. Furthermore, we highlight emerging therapeutic targets, such as dipeptidase 1 (DPEP1) and peptidyl arginine deiminase 4 (PAD4), and discuss the translational potential of precision immunomodulatory strategies. By elucidating the multi-dimensional roles of neutrophils, this review seeks to establish a precision, stage-specific framework for novel interventions in both acute kidney disease and CKDs.