Cozzolino Mario, Magagnoli Lorenza, Ciceri Paola
Department of Health Sciences, University of Milan, 20122 Milan, Italy.
Toxins (Basel). 2025 Jun 10;17(6):295. doi: 10.3390/toxins17060295.
Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on molecular weight and protein-binding properties to the 2023 multidimensional framework integrating clinical outcomes, clearance technologies, and artificial intelligence. We highlighted the toxicity mechanisms of UTs across the cardiovascular, immune, and nervous systems and evaluated traditional (e.g., low-/high-flux hemodialysis) and advanced (e.g., high-cutoff dialysis and hemoadsorption) clearance strategies. Despite progress, challenges persist in toxin detection, clearance efficiency, and personalized therapy. Future directions include multi-omics-based biomarker discovery, optimized dialysis membranes, advanced adsorption technology, and AI-driven treatment personalization. This synthesis aims to bridge translational gaps and guide precision medicine in nephrology.
慢性肾脏病（CKD）是一项全球性的健康负担，尿毒症毒素（UTs）在其病理生理学中起着核心作用。在本综述中，我们系统地研究了UT分类的演变，从基于分子量和蛋白结合特性的2003年欧洲尿毒症毒素工作组（EUTox）系统，到整合临床结局、清除技术和人工智能的2023年多维框架。我们强调了UTs在心血管、免疫和神经系统中的毒性机制，并评估了传统（如低通量/高通量血液透析）和先进（如高截留量透析和血液吸附）清除策略。尽管取得了进展，但在毒素检测、清除效率和个性化治疗方面仍存在挑战。未来的方向包括基于多组学的生物标志物发现、优化透析膜、先进吸附技术以及人工智能驱动的治疗个性化。本综述旨在弥合转化差距，并指导肾脏病学中的精准医学。
