Yao Peng, Zheng Ying, Li Cuicui
Department of Nephrology, The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, 610051, China.
Key Laboratory of Nuclear and Radiation Damage Mechanisms and Treatment Technologies at Chengdu Medical College of Sichuan Province, The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China.
Int Urol Nephrol. 2025 Sep 3. doi: 10.1007/s11255-025-04714-9.
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.
肾脏在急性损伤后具有显著的修复能力；然而，未加控制或持续的炎症通常会导致适应性不良的修复、纤维化，并进展为慢性肾脏病（CKD）。炎症在这一过程中起关键作用，其特征是不同免疫细胞群体与肾脏固有细胞之间存在复杂的双向交互作用。这种错综复杂的相互作用严重决定了成功再生与病理性瘢痕形成之间的平衡。本综述深入探讨了支撑肾脏损伤和适应性不良修复的基本免疫机制，分析了关键免疫细胞和肾脏固有细胞类型的具体作用、它们复杂的通讯网络以及关键信号通路。认识到传统全身治疗的局限性，我们广泛探索了纳米技术介导的药物递送系统在肾脏疾病靶向干预方面的新兴潜力。我们详细阐述了纳米颗粒物理化学性质的精确工程设计和主动靶向策略如何实现向特定肾内部位和细胞类型的靶向递送，克服生理屏障。此外，我们强调了纳米治疗在减轻急性肾损伤（AKI）中的氧化应激和炎症、对抗各种形式CKD的病理过程以及解决肾脏移植中的炎症挑战方面有前景的临床前进展。通过将对肾脏疾病复杂免疫病理学的见解与创新的纳米治疗策略相结合，本综述强调了开发更有效、靶向性更强和个性化治疗方法以改善患者预后的巨大潜力。
