Patients with chronic kidney disease (CKD) develop anemia largely because of inappropriately low erythropoietin (EPO) production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open-label, clinical trials in dialysis-dependent and non–dialysis-dependent patients with CKD and anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis-stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron-binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.

中文翻译：

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vadadustat 对慢性肾病相关性贫血患者的促红细胞生成作用

慢性肾病 (CKD) 患者之所以会出现贫血，主要是因为促红细胞生成素 (EPO) 的生成量过低以及红细胞前体可用的铁不足。在 CKD 和贫血透析依赖和非透析依赖患者中进行的四项 3 期随机、开放标签临床试验中，缺氧诱导因子脯氨酰羟化酶抑制剂 vadadustat 不劣于红细胞生成刺激剂 darbepoetin alfa，增加和维持目标血红蛋白浓度。在这些试验中，vadadustat 增加了血清 EPO 浓度、循环红细胞数量和循环网织红细胞数量。接受 vadadustat 或 darbepoetin alfa 治疗的患者达到的血红蛋白浓度相似，但与接受 darbepoetin alfa 治疗的患者相比，接受 vadadustat 的患者的红细胞平均红细胞体积和平均红细胞血红蛋白增加，而红细胞分布宽度减少。通过总铁结合能力测量的血清转铁蛋白浓度增加，加上稳定的血清铁浓度，导致随机分配至 vadadustat 的患者与随机分配至 darbepoetin alfa 的患者相比，转铁蛋白饱和度降低。与接受 darbepoetin alfa 的患者相比，转铁蛋白饱和度的降低与接受 vadadustat 的患者血清铁调素和铁蛋白的下降相对较大有关。血清转铁蛋白饱和度、铁调素、铁蛋白和红细胞指数的这些结果与接受 vadadustat 的患者的铁可用性提高一致。因此，总的来说，