From previous studies, the frequency of administration of recombinant human erythropoietin injection (rHuEPO) has no association with its therapeutic effect in renal anemia in chronic kidney disease (CKD), and there is no significant difference in the efficacy between weekly single dosing and divided dosing. Most hemodialysis patients are clinically treated with moderate-dose rHuEPO, but there is a lack of research on the safety of single and divided administration of moderate-dose rHuEPO.

To compare the safety between weekly single and divided administration of moderate-dose rHuEPO for renal anemia in maintenance hemodialysis patients.

This study was designed as a randomized, parallel-group controlled, non-inferiority clinical trial. Eighty-eight patients with renal anemia who underwent maintenance hemodialysis at the Hemodialysis Room, Tongzhou Branch, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2019 to May 2021 were selected and randomly divided into an experimental group and a control group with 44 in each. For comparing the safety and efficacy of weekly single and divided administration of moderate-dose rHuEPO, 29 cases (experimental subgroup 1) and other 15 cases (experimental subgroup 2) in the experimental group received an rHuEPO dose of 6 000 U, and an rHuEPO dose of 4 000 U, once a week, respectively; 30 cases (control subgroup 1) in the control group received a single rHuEPO dose of 2 000 U, three times a week (6 000 U per week in total), and other 14 cases (control subgroup 2) received a single rHuEPO dose of 2 000 U, twice a week (4 000 U per week in total) .

Safety analysis: two-factor repeated-measures ANOVA showed that the type of intervention scheme and duration had no interaction effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pre-dialysis serum potassium between experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 (P>0.05), and produced no main effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pre-dialysis serum potassium in experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 (P>0.05). The serum levels of AST, ALT and TBiL were similar between experimental subgroup 1 and control subgroup 1 at baseline and 12 weeks of treatment (P>0.05). Likewise, they were similar between experimental subgroup 2 and control subgroup 2 at baseline and 12 weeks of treatment (P>0.05). No thromboembolic, cardiovascular or cerebrovascular events and gastrointestinal reactions related to rHuEPO occurred in any of the subgroups during the 12-week treatment. Efficacy analysis: the hemoglobin level (reference range was 110-130 g/L) in experimental subgroup 1 〔65.5% (19/29) 〕was similar to that in control subgroup 1 〔73.3% (22/30) 〕at 12 weeks of treatment (χ^2=0.425, P=0.514). The serum levels of hemoglobin were similar between experimental subgroup 2 and control subgroup 2 at 12 weeks of treatment (P>0.05). The levels of red blood cell count, hematocrit, percentage and absolute number of reticulocytes, ferritin and transferrin saturation did not vary between experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 either at baseline or 12 weeks of treatment (P>0.05) .

Weekly single and divided administration of moderate-dose erythropoietin had no significant difference in medication safety in the treatment of renal anemia in maintenance hemodialysis patients.

既往研究表明重组人促红素注射液（rHuEPO）治疗慢性肾脏病（CKD）患者肾性贫血的给药频率不影响治疗效果，每周单次给药与分次给药疗效无明显差异，临床中大部分进行血液透析的患者使用中等剂量rHuEPO，而对于中等剂量rHuEPO单次给药与分次给药的安全性研究较欠缺。

探讨中等剂量rHuEPO每周单次与分次给药治疗维持性血液透析患者肾性贫血安全性差异。

本研究采用随机、平行对照、非劣效性临床试验设计。选取2019年1月至2021年5月于北京中医药大学东直门医院通州院区血透室进行维持性血液透析的88例肾性贫血患者，随机分为试验组和对照组，每组44例。试验组为rHuEPO每周单次给药，分为6 000 U/次且1次/周（试验1组，n=29）、4 000 U/次且1次/周（试验2组，n=15）两个亚组，对照组为rHuEPO每周分次给药，分为2 000 U/次且3次/周（对照1组，n=30）、2 000 U/次且2次/周（对照2组，n=14）两个亚组。比较试验组与对照组的安全性指标及疗效指标。

安全性指标：两因素重复测量方差分析结果显示，组间与时间对试验1组与对照1组，试验2组与对照2组患者的收缩压、舒张压、平均动脉压、透前血钾不存在交互作用（P>0.05），组间、时间对试验1组与对照1组，试验2组与对照2组患者的收缩压、舒张压、平均动脉压、透前血钾主效应不显著（P>0.05）；治疗前、治疗12周，试验1组与对照1组、试验2组与对照2组患者天冬氨酸氨基转移酶、丙氨酸氨基转移酶、总胆红素比较，差异均无统计学意义（P>0.05）；治疗12周，各组患者均未出现血栓栓塞、心脑血管事件及与rHuEPO相关的胃肠道反应。疗效指标：治疗12周试验1组患者血红蛋白水平（参考范围：110~130 g/L）不劣于对照1组〔65.5%（19/29）和73.3%（22/30），χ^2=0.425，P=0.514〕；治疗12周试验2组和对照2组患者血红蛋白水平比较，差异无统计学意义（P>0.05）；治疗前、治疗12周，试验1组与对照1组、试验2组与对照2组患者红细胞计数、血细胞比容、网织红细胞百分比、网织红细胞绝对值、血清铁蛋白、转铁蛋白饱和度比较，差异无统计学意义（P>0.05）。

中等剂量（4 000~6 000 U）rHuEPO每周单次给药治疗维持性血液透析患者肾性贫血与分次给药在安全性方面无明显差异。