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罗沙司他治疗红细胞生成素低反应性透析患者:一项单中心前瞻性研究。

Roxadustat for dialysis patients with erythropoietin hypo-responsiveness: a single-center, prospective investigation.

机构信息

Department of Blood Purification Center, Nanjing First Hospital, Nanjing Medical University, No. 68 Changle Road, Qinhuai District, Nanjing, 210006, Jiangsu, China.

Department of Healthcare-Associated Infection Management, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

出版信息

Intern Emerg Med. 2021 Nov;16(8):2193-2199. doi: 10.1007/s11739-021-02738-4. Epub 2021 May 22.

Abstract

Dialysis patients with erythropoietin hypo-responsiveness suffered from refractory anemia. Roxadustat reversibly binds and inhibits hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD), resulting in increased endogenous EPO which stimulates erythropoiesis, theoretically has an advantage over exogenous EPO in anti-anemia therapy. From September 2019 to October 2020, 32 dialysis patients with hypo-responsiveness to erythropoietin were evaluated. During the 24-week follow-up period, all patients were taken off erythropoietin and switched to roxadustat. Dosage adjustments were administrated according to the fluctuation of hemoglobin level during the treatment. Parameters about anemia, iron metabolism and biochemical indexes were collected, and adverse events were recorded. A total of 31 patients completed the clinical observation, with varying degrees of malnutrition-inflammation. Post treatment, the levels of transferrin and total iron-binding capacity were increased, while that of transferrin saturation and cholesterol decreased. 15 cases (accounting for 48.39%, designated as fulfilled group) met the target level of hemoglobin, while 16 cases (51.61%, non-fulfilled group) did not. The baseline conditions of the above two groups were compared. The levels of hypersensitive C-reactive protein, interleukin-6 and serum ferritin in the non-fulfilled group were higher than those in the fulfilled group, and the levels of residual renal function, serum albumin, iron, transferrin and total iron-binding capacity were lower than those in the fulfilled group. Linear regression analysis showed that increase of HsCRP had a negative effect on the improvement of Hb. One case of adverse reaction grade 3 and four cases of grade 2 occurred throughout the study, yet all were relieved after therapy. Significant anti-anemia effects could be achieved in most patients with erythropoietin hypo-responsiveness after treatment with roxadustat, accompanied by relatively mild and rare adverse reactions. The malnutrition-inflammation states of patients may interfere with the anti-anemia effect of roxadustat, and iron utilization is more important than iron storage in anemia improvement.

摘要

接受促红细胞生成素治疗反应低下的透析患者患有难治性贫血。罗沙司他可逆地结合并抑制低氧诱导因子脯氨酰羟化酶(HIF-PHD),从而增加内源性 EPO,刺激红细胞生成,理论上在抗贫血治疗中优于外源性 EPO。2019 年 9 月至 2020 年 10 月,评估了 32 例对促红细胞生成素反应低下的透析患者。在 24 周的随访期间,所有患者停用促红细胞生成素并换用罗沙司他。根据治疗期间血红蛋白水平的波动进行剂量调整。收集贫血、铁代谢和生化指标参数,并记录不良反应。共有 31 例患者完成了临床观察,存在不同程度的营养不良-炎症。治疗后,转铁蛋白和总铁结合力水平升高,而转铁蛋白饱和度和胆固醇水平降低。15 例(占 48.39%,达标组)达到血红蛋白目标水平,而 16 例(51.61%,未达标组)未达到。比较两组的基线情况。未达标组超敏 C 反应蛋白、白细胞介素-6 和血清铁蛋白水平高于达标组,残余肾功能、血清白蛋白、铁、转铁蛋白和总铁结合力水平低于达标组。线性回归分析显示,HsCRP 升高对 Hb 改善有负面影响。研究过程中发生 1 例不良反应 3 级和 4 例 2 级,经治疗后均缓解。罗沙司他治疗后,大多数促红细胞生成素反应低下的患者可获得显著的抗贫血效果,且不良反应相对较轻且少见。患者的营养不良-炎症状态可能会干扰罗沙司他的抗贫血效果,铁的利用比铁的储存对贫血的改善更为重要。

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