Aizawa Ken, Kawasaki Ryohei, Tashiro Yoshihito, Shimonaka Yasushi, Hirata Michinori
Product Research Department, Chugai Pharmaceutical Co., Ltd, 200 Kajiwara, Kamakura, 247-8530, Japan.
BMC Nephrol. 2018 Jan 27;19(1):19. doi: 10.1186/s12882-018-0818-4.
Epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) is currently widely used for the treatment of anemia associated with chronic kidney disease (CKD). Therapeutic control of anemia is assessed by monitoring haemoglobin (Hb) levels. However, certain qualitative aspects of erythrocytes are also impaired in CKD, including loss of deformability and shortened life-span. Therefore, monitoring Hb alone could potentially fail to reveal pathological changes in erythrocytes. Focusing on erythrocyte quality in CKD may lead to more effective anemia therapy with C.E.R.A.
A CKD rat model was induced by uninephrectomy followed by anti-Thy1.1 antibody injection. From 5 weeks after the operation, C.E.R.A. (0.6 μg/kg) or vehicle was administered every 2 weeks. Erythrocyte deformability was quantified with ektacytometry and erythrocyte turnover was estimated by biotin labeling. Intracellular calcium level was assessed by Fluo-3/AM.
Erythrocyte deformability progressively declined in CKD rats. Furthermore, erythrocyte turnover in the circulation drastically accelerated in CKD rats. With administration of C.E.R.A. at a dose sufficient to adequately control Hb, deterioration of erythrocyte deformability and turnover in CKD rats were significantly improved. Intracellular calcium, which plays a pivotal role in the mediation of erythrocyte quality, was significantly increased in CKD and was normalized by C.E.R.A.
C.E.R.A. treatment exerted a favorable effect not only on anemia but also on the improvement of erythrocyte quality. C.E.R.A. administered for the treatment of CKD-associated anemia may confer therapeutic benefits on erythrocytes.
聚乙二醇化促红细胞生成素β（持续促红细胞生成素受体激活剂；C.E.R.A.）目前广泛用于治疗与慢性肾脏病（CKD）相关的贫血。通过监测血红蛋白（Hb）水平评估贫血的治疗控制情况。然而，CKD患者的红细胞某些质量方面也会受损，包括变形性丧失和寿命缩短。因此，仅监测Hb可能无法揭示红细胞的病理变化。关注CKD患者的红细胞质量可能会使C.E.R.A.治疗贫血更有效。
通过单侧肾切除术后注射抗Thy1.1抗体诱导建立CKD大鼠模型。术后5周起，每2周给予C.E.R.A.（0.6μg/kg）或赋形剂。用激光衍射法测定红细胞变形性，通过生物素标记估计红细胞周转率。用Fluo-3/AM评估细胞内钙水平。
CKD大鼠的红细胞变形性逐渐下降。此外，CKD大鼠循环中的红细胞周转率急剧加快。给予足以充分控制Hb的剂量的C.E.R.A.后，CKD大鼠红细胞变形性和周转率的恶化得到显著改善。在介导红细胞质量方面起关键作用的细胞内钙在CKD中显著升高，并通过C.E.R.A.恢复正常。
C.E.R.A.治疗不仅对贫血有良好效果，而且对改善红细胞质量也有作用。用于治疗CKD相关贫血的C.E.R.A.可能对红细胞有治疗益处。
