Precision nanotherapeutics for kidney disease: targeting inflammation and maladaptive repair

The kidney exhibits a remarkable capacity for repair following acute injury; however, unchecked or persistent inflammation often drives maladaptive repair, fibrosis, and progression to chronic kidney disease (CKD). Inflammation is pivotal in this process, characterized by complex, bidirectional cross talk between diverse immune cell populations and resident renal intrinsic cells. This intricate interplay critically dictates the balance between successful regeneration and pathological scarring. This review delves into the fundamental immunologic mechanisms underpinning kidney injury and maladaptive repair, analyzing the specific roles of key immune and intrinsic renal cell types, their complex communication networks, and critical signaling pathways. Recognizing the limitations of conventional systemic therapies, we extensively explore the emerging potential of nanotechnology-mediated drug delivery systems for targeted interventions in kidney diseases. We detail how the precise engineering of nanoparticle physicochemical properties and active targeting strategies enables targeted delivery to specific intrarenal sites and cell types, overcoming physiological barriers. Furthermore, we highlight promising preclinical advancements of nanotherapeutics designed to mitigate oxidative stress and inflammation in AKI, counteract pathological processes in various forms of CKD, and address inflammatory challenges in kidney transplantation. By integrating insights into the complex immunopathology of kidney disease with innovative nanotherapeutic strategies, this review underscores the significant potential for developing more effective, targeted, and personalized treatments to improve patient outcomes.