Kanbay Mehmet, Copur Sidar, Yilmaz Zeynep Y, Mallamaci Francesca, Zoccali Carmine
Division of Nephrology, Department of Medicine, Koc University School of Medicine, 34010, Istanbul, Turkey.
Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
J Nephrol. 2025 Mar;38(2):403-414. doi: 10.1007/s40620-024-02117-0. Epub 2024 Oct 25.
Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.
慢性肾脏病贫血是一种继发于多种病因的多因素病症，这些病因包括营养缺乏、慢性炎症、促红细胞生成素缺乏或抵抗、骨髓抑制、缺铁以及药物不良反应。慢性肾脏病患者贫血的主要治疗干预措施是促红细胞生成剂。然而，促红细胞生成剂的一个局限性是存在血栓栓塞事件、高血压、癫痫发作、实体器官恶性肿瘤以及反应低下的风险。一种新型白细胞介素-6单克隆抗体——齐特昔单抗，已在初步临床试验中对慢性肾脏病患者的贫血管理进行了评估，结果令人鼓舞，包括血红蛋白水平的改善和炎症参数的降低。这些试验表明，与其他靶向白细胞介素-6的单克隆抗体（如托珠单抗）不同，齐特昔单抗不会增加血细胞减少或感染并发症的风险。此外，有报道称其对血清脂质谱有潜在的有益影响，从而产生了该药物对动脉粥样硬化并发症有有利影响的假设。此外，齐特昔单抗在改善贫血参数（包括血红蛋白水平和铁代谢指标）方面已显示出疗效。齐特昔单抗值得进行全面的临床开发，为此，大规模临床试验正在进行中。
