尿毒症蛋白结合毒素与肾性贫血的关系研究 进展

Research Progress on the Relationship between Uremic Protein-Bound Toxins and Renal Anemia

摘要: 肾性贫血是慢性肾脏病(chronic kidney disease, CKD)患者的常见并发症，传统观点认为其主要由促红细胞生成素(Erythropoietin, EPO)绝对或相对不足所致。然而，临床实践中观察到部分患者对EPO治疗反应不佳，提示尿毒症环境中存在独立于EPO缺乏的致病因素。蛋白结合尿毒症毒素(protein-bound uremic toxins, PBUTs)因与白蛋白高亲和结合、难以通过常规透析清除，可在体内持续蓄积并通过多种机制干扰红系生成、加重炎症与氧化应激，成为肾性贫血研究的新热点。本文系统综述PBUTs的定义、来源、代谢特点，阐述其直接抑制红系生成、诱导氧化应激、炎症、影响药物处置及作为远程信号分子参与多器官互作的致贫血机制，总结临床相关性证据及现有干预策略，并探讨未来研究方向，旨在为深入理解PBUTs在肾性贫血中的作用及开发新型治疗策略提供理论依据。

Abstract: Renal anemia is a common complication in patients with chronic kidney disease (CKD). The traditional view holds that it is mainly caused by absolute or relative deficiency of erythropoietin (EPO). However, clinical practice has observed poor response to EPO treatment in some patients, suggesting the presence of pathogenic factors independent of EPO deficiency in the uremic environment. Protein-bound uremic toxins (PBUTs), due to their high affinity binding with albumin and difficulty in being removed by conventional dialysis, can accumulate continuously in the body and interfere with erythropoiesis through multiple mechanisms, exacerbating inflammation and oxidative stress, becoming a new hotspot in renal anemia research. This article systematically reviews the definition, sources, and metabolic characteristics of PBUTs, elaborates their mechanisms of directly inhibiting erythropoiesis, inducing oxidative stress and inflammation, affecting drug disposition, and participating in multi-organ interactions as remote signaling molecules. The article summarizes clinical correlation evidence and existing intervention strategies, and explores future research directions, aiming to provide a theoretical basis for understanding the role of PBUTs in renal anemia and developing novel therapeutic strategies.