目的 观察罗沙司他代替重组人红细胞生成素(recombinant human erythropoietin，rhEPO)在维持性透析患者肾性贫血治疗的效果。 方法 收集2020年8月～2021年10月徐州医科大学附属医院收治的维持性透析合并肾性贫血的患者21例，根据体质量及贫血程度应用相应剂量rhEPO至少3个月但血红蛋白仍小于100g/L，改用罗沙司他治疗，平均随访时间24周，分析患者治疗前后相关指标的变化。 结果 罗沙司他治疗4周、8周、12周、16周、20周、24周红细胞计数、血红蛋白、红细胞比容均较治疗前升高(F值分别为10.290、9.053、9.858，均P＜0.001)。罗沙司他治疗后网织红细胞计数从第4周开始升高，第8周、12周、24周较治疗前差异有统计学意义(F=6.031，P＜0.001)。罗沙司他治疗12周、24周总铁结合力升高(F=9.336，P=0.002)，总胆固醇、低密度脂蛋白均降低(F值分别为14.200、12.090，均 P＜0.001)。罗沙司他治疗后网织红细胞百分比、网织红细胞血红蛋白含量、未成熟网织红细胞比率、血清铁、铁蛋白、转铁蛋白饱和度、红细胞生成素(erythropoietin，EPO)等均较治疗前差异无统计学意义 (F/t值分别为0.881、3.067、0.476、3.629、2.783、1.910、-1.020，P值分别为0.421、0.057、0.679、0.067、0.093、0.158、0.315)。 结论 在维持性透析合并肾性贫血患者应用rhEPO治疗效果欠佳的患者改用罗沙司他治疗可有效改善贫血及脂代谢，不良反应较少。
Objective To observe the use of Roxadustat to replace recombinant human erythropoietin (rhEPO) in the treatment of renal anemia in maintenance dialysis (MHD) patients. Methods Twenty-one MHD patients complicated with renal anemia and treated in The Affiliated Hospital of Xuzhou Medical University during August 2020 to October 2021 were enrolled in this study. They were treated with rhEPO using the dose based on body mass and anemia degree for at least 3 months, but their hemoglobin continued to be <100g/L. Roxadustat was then used to replace rhEPO therapy. They were followed up for an average period of 24 weeks. Their clinical indicators were compared before and after Roxadustat therapy. Results After 4, 8, 12, 16, 20 and 24 weeks of Roxadustat therapy, RBC count, hemoglobin and RBC specific volume became higher(F=10.290, 9.053 and 9.858 respectively;P＜0.001); reticulocyte count increased beginning from the 4th week, and the differences were statistically significant at the 8th, 12th and 24th weeks (F=6.031, P＜0.001) as compared with that before the Roxadustat therapy; total iron binding capacity increased after 12 and 24 weeks of Roxadustat therapy (F=9.336, P=0.002); total cholesterol and low density lipoprotein decreased (F=14.200 and 12.090; P＜0.001). After Roxadustat therapy, reticulocyte percentage, hemoglobin content in reticulocytes, immature reticulocyte ratio, serum iron, ferritin, transferrin saturation and erythropoietin (EPO) level remained unchanged as compared with those before Roxadustat therapy (F=0.881, 3.067, 0.476, 3.629, 2.783 and 1.910, and t=-1.020 respectively; P=0.421, 0.057, 0.679, 0.067, 0.093, 0.158 and 0.315 respectively). Conclusions In MHD patients complicated with renal anemia and poor responses to rhEPO treatment, Roxadustat can effectively improve anemia and lipid metabolism, with less adverse reactions.
1.Hill NR,Fatoba ST,Oke JL,et al.Global prevalence of chronic kidney disease-a systematic review and Meta-analysis[J].PLos One,2016，11(7):e0158765.
2.Chen N,Hao C,Liu BC,et a1.Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.N EngI J Med,2019,381(11):101l-1022.
3.何琴,蔡宏,张伟明,维持性血液透析患者贫血状况与预后的关系.中华肾脏病杂志,2016,32(2):110 -117.
4.Babitt JL，Lin HY.Mechanisms of anemia in CKD[J].J Am Soc Nephrol,2012,23(10):1631-1634.
5.Begum S,Latunde-Dada G O.Anemia of inflammation with an emphasis on chronic kidney disease [J].Nutrients，2019，11(10):2424.
6.Vecchio LD,Minutolo R.ESA iron therapy and new drugs: are there new perspectives in the treatment of anaemia[J].J Clin Med，2021，10(4):839.
7.Sch?del J,Ratcliffe PJ.Mechanisms of hypoxia signalling: new implications for nephrology[J].Nat Rev Nephrol,2019,15(10):641-659.
8.付玉琪,涂岩,刘必成.低氧诱导因子-脯氨酸羟化酶抑制剂治疗肾性贫血的研究进展[J].中华肾脏病杂志,2020,36(9):726-730.
9.Akizawa T,Iwasaki M,Yamaguchi Y,et al.Phase 3,Randomized,Double-Blind,Active-Comparator(Darbepoetin Alfa)Study of 0ral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan.J Am Soc Nephrol,2020,31(7):1628-1639.
10. 中华医学会肾脏病学分会肾性贫血诊断和治疗共识专家组.肾性贫血诊断与治疗中国专家共识(2018修订版)[J].中华肾脏病杂志,2018,34(11):860-866.
11. Groenendaal-Van De Meent D,Den Adel M,Van Dijk J,et al.Effect of multiple doses of omeprazole on the pharmacokinetics,safety,and tolerability of roxadustat in healthy subjects[J].Eur J Drug Metab Pharmacokinet,2018,43(6):685-692.
12. Chen N,Qian J,Chen J,et al.Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China [J].Nephrol Dial Transplant,2017,32(8):1373-1386.
13. Coyne DW,Roger SD,Shin SK,et al.Roxadustat for CKD-related anemia in non-dialysis patients[J].Kidney Int Rep,2020,6(3):624-635.
14. 中国医师协会肾脏内科医师分会肾性贫血指南工作组.中国肾性贫血诊治临床实践指南[J].中华医学杂志,2021,101(20):1463-1502.
15. Liu J, Zhang A, Hayden JC, et al. Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: a systematic review and meta-analysis. [J]. Pharmacological research,2020,155:104747.
16.Akizawa T, Otsuka T, Reusch M, et al. Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open-Label Study. [J]. Ther Apher Dial,2020,24(2):115-125.
17.Haase VH, Chertow GM, Block GA, et al. Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. [J].Nephrol Dial Transplant:2019,34(1):90-99.
18. Besarab A, Chernyavskaya, E, Motylev I, et al. Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. [J].J Am Soc Nephrol:2016,27(4):1225-33.
19. Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis[J]. N Engl J Med,2019,381(11)：1001-1010.
20. Grzeszczak W, Szczyra D, Snit M. Whether Prolyl Hydroxylase Blocker-Roxadustat-In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future？Int J Environ Res Public Health,2021,18(4):1612.
