Li Zuolin, Shen Lan, Tu Yan, Lu Shun, Liu Bicheng
Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu 210009, China.
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Chin Med J (Engl). 2025 Jun 20;138(12):1424-1432. doi: 10.1097/CM9.0000000000003470. Epub 2025 May 23.
Anemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin (EPO) production and iron absorption and utilization. Thus, HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism. Here, we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD. Specifically, we highlighted the key features of HIF-PHIs on ACD, such as stimulation of endogenous EPO, handling iron metabolism, inflammation-independent, and prolonging lifespan of red blood cells. In conclusion, the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.
慢性病贫血（ACD）是慢性病患者中最常见的临床问题。ACD通常继发于慢性肾脏病（CKD）、癌症和慢性感染，与不良健康结局、发病率和死亡率增加以及巨大的经济成本相关。目前针对ACD的治疗选择非常有限。缺氧诱导因子-脯氨酰羟化酶（HIF-PHD）途径的发现使得开发新型治疗药物（如缺氧诱导因子-脯氨酰羟化酶抑制剂，HIF-PHI）成为可能，通过稳定HIF并随后促进内源性促红细胞生成素（EPO）的产生以及铁的吸收和利用来治疗ACD。因此，HIF-PHIs似乎为以新机制治疗ACD患者打开了一扇新的大门。在此，我们全面综述了HIF-PHIs在ACD应用中的最新进展。具体而言，我们强调了HIF-PHIs对ACD的关键特性，如刺激内源性EPO、调节铁代谢、不依赖炎症以及延长红细胞寿命。总之，HIF-PHIs在治疗ACD方面的成功可能会为除肾性贫血之外的其他类型贫血扩大治疗机会。
