Department of Health Sciences, "Magna Graecia" University, I-88100 Catanzaro, Italy.
Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Viale Europa, I-88100 Catanzaro, Italy.
Int J Mol Sci. 2021 Nov 22;22(22):12590. doi: 10.3390/ijms222212590.
Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.
贫血是慢性肾脏病（CKD）的常见并发症。随着估算肾小球滤过率（eGFR）的降低，CKD 患者贫血的患病率显著增加。CKD 患者贫血的病理生理学较为复杂。主要原因是促红细胞生成素（EPO）缺乏和功能性铁缺乏（FID）。目前，对于透析和非透析患者，使用注射用重组红细胞生成刺激剂（ESA），尤其是促红细胞生成素和达贝泊汀，并联合口服或静脉（iv）铁剂补充，是治疗 CKD 贫血的方法。这种方法可以减少患者对输血的依赖，确保达到最佳的血红蛋白目标水平。然而，目前尚无证据表明使用 ESA 治疗贫血可以显著降低心血管事件的风险。同时，iv 铁剂补充会增加过敏反应、胃肠道副作用、感染和心血管事件的风险。目前，尚无研究确定使用 ESA 的最佳策略以最小化可能的风险。正在评估的一类药物，即脯氨酰羟化酶抑制剂（PHIs），通过抑制脯氨酰羟化酶（PH）酶来稳定低氧诱导因子（HIF）。几项随机对照试验表明，HIF-PHIs 几乎与 ESA 相当。在个性化医学时代，可以根据个体的风险状况和作用机制，设想并研究 HIF 稳定剂的具体应用场景。
