Efficacy of Roxadustat in the Maintenance Hemodialysis of HIV/AIDS Patients Resistant to EPO
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摘要:
目的 观察罗沙司他治疗促红细胞生成素(erythropoietin,EPO)抵抗的维持性血透HIV/AIDS患者的临床疗效和安全性。 方法 将2022年7月至2023年12月在昆明市第三人民医院血液净化中心行维持性血透治疗的HIV/AIDS合并EPO抵抗患者60例,根据患者意愿分为继续使用重组促红细胞生成素(EPO)治疗的对照组30例,使用罗沙司他治疗的观察组30例,治疗8周。记录比较2组治疗前后患者的血红蛋白(HGB)、铁蛋白(SF)、血清铁(SI)、总铁结合力(TIBC)、超敏C反应蛋白(hs-CRP)、细胞因子(IL-1β、IL-6、IL-8、IL-10、TNF-α、IFN-γ、IFN-α)指标,并监测药物不良反应发生情况。 结果 观察组患者治疗8周后血红蛋白(HGB)、血清铁(SI)、总铁结合力(TIBC)水平均显著升高,差异均有统计学意义(均P < 0.05),铁蛋白(SF)、IL-1β、IL-6、IL-10、TNF-α水平均显著下降,差异均有统计学意义(均P < 0.05);2组组间比较,观察组患者血红蛋白(HGB)、总铁结合力(TIBC)水平均高于对照组,差异均有统计学意义(均P < 0.05),观察组铁蛋白(SF)、IL-1β、IL-6、IL-10、TNF-α水平均低于对照组,差异均有统计学意义(P < 0.05)。2组均无严重不良反应发生。 结论 对EPO抵抗的维持性血透HIV/AIDS患者使用罗沙司他安全有效,可明显改善患者血红蛋白及铁代谢水平,可以改善患者的微炎症状态。 Abstract:Objective To study the clinical efficacy and safety of Roxadustat in the maintenance hemodialysis of HIV/AIDS patients with EPO resistance. Methods 60 cases of HIV/AIDS patients with EPO resistance undergoing maintenance hemodialysis treatment at the Blood Purification Center of the Third People's Hospital of Kunming from July 2022 to December 2023 were divided based on patient preference into a control group of 30 cases continuing Erythropoietin (EPO) treatment and an observation group of 30 cases treated with Roxadustat for 8 weeks. Changes in patients' hemoglobin (HGB), serum ferritin (SF), serum iron (SI), total iron binding capacity (TIBC), high-sensitivity C-reactive protein (hs-CRP), cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, IFN-α) were recorded and compared before and after treatment in the two groups, along with monitoring the occurrence of adverse drug reactions. Results After 8 weeks of treatment, the levels of hemoglobin (HGB), serum iron (SI) and total iron binding capacity (TIBC) in observation group were significantly increased, and the differences were statistically significant (all P < 0.05), while the levels of serum ferritin (SF), IL-1β, IL-6, IL-10 and TNF-α were significantly decreased, with statistically significant (all P < 0.05). In the comparison between the two groups, the levels of hemoglobin (HGB) and total iron binding capacity (TIBC) in the observation group were higher than those in the control group, with statistically significant differences (all P < 0.05). The levels of serum iron (SF), IL-1β, IL-6, IL-10, and TNF-α in the observation group were lower than those in the control group, with statistically significant differences (P < 0.05). There were no serious adverse reactions in either group. Conclusion The use of Roxadustat in maintenance hemodialysis patients resistant to EPO and living with HIV/AIDS is safe and effective, significantly improving the patients' hemoglobin and iron metabolism levels, and can improve the patients' state of micro-inflammation. -
Key words:
- Roxadustat /
- EPO resistance /
- AIDS /
- Maintenance hemodialysis /
- Renal anemia
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表 1 2组患者治疗前的临床一般资料比较[n(%)/($\bar x \pm s $)/ M(Q1,Q3)]
Table 1. Comparison of general clinical data before treatment between the two groups [n(%)/($\bar x \pm s $)/ M(Q1,Q3)]
组别 男性 年龄(岁) 透析龄(月) 原发病HIV/AIDS相关性肾病 糖尿病肾病 高血压肾病 慢性肾小球肾炎 观察组(n = 30) 18(60.00) 49.40 ± 8.78 19.50 (14.25) 12(40.00) 5(16.67) 3(10.00) 10(33.33) 对照组(n = 30) 16(53.33) 49.87 ± 7.12 21.00(22.50) 9(30.00) 7(23.33) 5(16.67) 9(30.00) t/Z/χ2 0.271 −0.226 −0.481 0.659 0.417 0.144 0.077 P 0.602 0.822 0.630 0.417 0.519 0.704 0.781 表 2 组患者用药前后血红蛋白和铁代谢对比($\bar x \pm s $)
Table 2. Comparison of hemoglobin and iron metabolism between the two groups before and after treatment($\bar x \pm s $)
组别 HGB(g/L) 铁蛋白(ng/mL) 血清铁(μmol/L) 总铁结合力(μmol/L) 0周 8周 0周 8周 0周 8周 0周 8周 观察组(n = 30) 89.53 ± 7.84 97.53 ± 7.77* 124.31 ± 74.85 93.96 ± 52.96* 8.70 ± 3.51 10.40 ± 4.25* 42.89 ± 13.01 51.25 ± 12.75* 对照组(n = 30) 86.40 ± 6.02 91.57 ± 6.13* 128.38 ± 55.06 125.49 ± 53.98 9.88 ± 3.64 10.24 ± 3.81 42.91 ± 9.62 44.79 ± 9.96* t 1.736 3.303 −0.240 −2.284 −1.279 0.154 −0.006 2.187 P 0.088 0.002△ 0.811 0.026△ 0.206 0.878 0.996 0.033△ 2组用药后比较,△P < 0.05;同组用药后比较,*P < 0.05。 表 3 2组患者用药前后细胞因子比较($ \bar x \pm s $)
Table 3. Comparison of cytokines before and after treatment between the two groups($ \bar x \pm s $)
指标 时段 观察组(n = 30) 对照组(n = 30) t P IL-1β(pg/mL) 0周 2.95 ± 1.28 2.40 ± 1.14 1.763 0.083 8周 1.68 ± 1.01 2.36 ± 1.08 −2.529 0.014△ t 6.686 0.154 P < 0.001* 0.878 IL-6(pg/mL) 0周 9.54 ± 3.19 8.38 ± 3.27 1.393 0.169 8周 6.57 ± 2.48 8.09 ± 3.07 −2.115 0.039△ t 5.975 1.215 P < 0.001* 0.234 IL-8(pg/mL) 0周 31.16 ± 16.34 24.98 ± 10.77 1.728 0.090 8周 26.57 ± 13.68 23.89 ± 10.28 0.858 0.395 t 1.468 1.402 P 0.153 0.171 IL-10(pg/mL) 0周 8.66 ± 3.62 8.35 ± 3.29 0.344 0.732 8周 5.17 ± 2.87 7.74 ± 3.50 −3.108 0.003△ t 4.107 0.790 P < 0.001* 0.436 IFN-γ(pg/mL) 0周 6.23 ± 2.46 5.66 ± 2.25 0.921 0.361 8周 5.14 ± 2.67 5.62 ± 1.63 −0.841 0.405 t 1.818 0.104 P 0.079 0.918 IFN-α(pg/mL) 0周 4.41 ± 1.76 4.24 ± 1.65 0.366 0.716 8周 4.26 ± 1.93 3.65 ± 1.53 1.360 0.179 t 0.317 1.412 P 0.753 0.169 TNF-α(pg/mL) 0周 3.92 ± 1.73 4.56 ± 1.81 −1.392 0.169 8周 2.40 ± 1.01 4.06 ± 1.84 −4.350 < 0.001△ t 4.294 1.255 P < 0.001* 0.219 hs-CRP(mg/L) 0周 3.67 ± 1.54 3.10 ± 1.41 1.512 0.136 8周 3.24 ± 1.37 2.89 ± 1.40 0.978 0.332 t 1.243 1.136 P 0.224 0.265 2组用药后比较,△P < 0.05;同组用药后比较,*P < 0.05。 表 4 2组患者不良反应发生情况[n(%)]
Table 4. The occurrence of adverse reactions in two groups[n(%)]
组别 血压升高 血栓形成 过敏反应 胃肠道反应 不良反应 观察组(n = 30) 0(0) 2(6.67) 0 2(6.67) 4(13.33) 对照组(n = 30) 2(6.67) 3(10) 0 0 5(16.67) χ2 0.517 0.000 − 0.517 0.000 P 0.472 1.000 − 0.472 1.000 -
[1] 中华预防医学会肾脏病预防与控制专业委员会. 中国慢性肾脏病早期评价与管理指南[J]. 中华内科杂志,2023,62(8):902-930. doi: 10.3760/cma.j.cn112138-20221013-00755 [2] Chang R K,Juan J,Liang,et al. Burden of chronic kidney disease and its risk-attributable burden in 137 low-and middle-income countries,1990-2019: Results from the global burden of disease study 2019[J]. BMC Nephrology,2022,23(1):17. doi: 10.1186/s12882-021-02597-3 [3] 欣怡,胡章学. 人类免疫缺陷病毒感染伴肾病患者的临床病理分析[J]. 中华实验和临床感染病杂志,2020,14(1):78-82. [4] 李航,张福杰,卢洪洲,等. HIV感染合并慢性肾脏病患者管理专家共识[J]. 中国艾滋病性病,2017,23(6):578-580. [5] Abebe M,Belete,Taklo S,et al. Chronic kidney disease and associated factors among HIV infected patients taking tenofovir disoproxil fumarate based regimen in Ethiopia: A hospital-based cross-sectional study[J]. HIV/AIDS(Auckland,N. Z. ),2021,13:301-306. [6] Cao Y,Gong M,Han Y,et al. Prevalence and risk factors for chronic kidney disease among HIV‐infected antiretroviral therapy‐naïve patients in mainland China: A multicenter cross‐sectional study[J]. Nephrology,2013,18(4):307-312. doi: 10.1111/nep.12031 [7] Chi Y C,Kim M W,Man P L,et al. Prevalence of chronic kidney disease in Chinese HIV-infected patients[J]. Nephrology Dialysis Transplantation,2007,22(11):3186-3190. doi: 10.1093/ndt/gfm350 [8] 中华医学会感染病学分会艾滋病丙型肝炎学组,中国疾病预防控制中心. 中国艾滋病诊疗指南(2018年版)[J]. 中华内科杂志,2018,57(12): 867-884. [9] 孟磊,丁文惠,史力斌,等. 慢性肾脏病患者发生心血管事件危险因素的研究[J]. 中华心血管病杂志,2009,37(1):53-55. [10] KDIGO Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease[J]. Kidney Int Suppl,2012,2(4):279-335. doi: 10.1038/kisup.2012.37 [11] 霍岩,丁海波,耿文清. HIV感染者贫血的发病机制和临床管理策略[J]. 中国艾滋病性病,2022,28(10):1215-1218. [12] 中国医师协会肾脏内科医师分会肾性贫血指南工作组. 中国肾性贫血诊疗的临床实践指南[J]. 中华医学杂志,2021,101(20):1463-1502. doi: 10.3760/cma.j.cn112137-20210201-00309 [13] 李蓉生. 慢性病贫血[J]. 中华检验医学杂志,2011,34(2):190-192. doi: 10.3760/cma.j.issn.1009-9158.2011.02.025 [14] 上海法默生物科技有限公司. 一种罗沙司他中间体的制备方法: CN202110313892.0[P]. 2021-07-06. [15] 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. doi: 10.3760/cma.j.issn.1001-7097.2018.11.012 [16] 董淑英,焦军东,李春媚. 促红细胞生成素抵抗原因及治疗研究进展[J]. 中国中西医结合肾病杂志,2011,12(11):1033-1034. doi: 10.3969/j.issn.1009-587X.2011.11.031 [17] Elliott J,Mishler D,Agarwal R. Hyporesponsiveness to erythropoietin: Causes and management[J]. Adv Chronic Kidney Dis,2009,16(2):94-100. doi: 10.1053/j.ackd.2008.12.004 [18] 王丽珍. 铁状况与HIV感染结局[J]. 国外医学(医学地理分册),2002,23(3):133-134. doi: 10.3969/j.issn.1001-8883.2002.03.015 [19] 王睿,胡洪涛,胡双,等. 罗沙司他治疗慢性肾脏分析[J]. 临床肾脏病杂志,2019,19(12):871-876. [20] 郑光毅,洪大情,李贵森,等. 罗沙司他对不同铁代谢状态维持性血液透析患者贫血的影响[J]. 肾脏病与透析肾移植杂志,2021,30(6):536-540. doi: 10.3969/j.issn.1006-298X.2021.06.007 [21] 周慧友. HIF-PHIs对慢性肾衰竭合并地中海贫血患者贫血疗效及铁代谢的影响[D]. 海口: 海南医学院,2023. [22] 申芳丽,宋沧桑,李兴德,等. 罗沙司他治疗肾性贫血的临床应用研究进展[J]. 中国新药杂志,2022,31(18):1815-1822. doi: 10.3969/j.issn.1003-3734.2022.18.010 [23] 李锦龙,胡玉刚,周青. 慢性肾脏病患者主要心血管不良事件危险因素的临床研究与进展[J]. 临床肾脏病杂志,2022,22(11):959-966. doi: 10.3969/j.issn.1671-2390.2022.11.013 [24] Lu J,Ma S,Zhang W Y,et al. AIDS和HIV阳性个体外周血炎症因子(TNF-α和IL-6)和肠道菌群的变化研究(英文)[J]. Journal of Zhejiang University-Science B(Biomedicine & Biotechnology),2019,20(10):793-802. [25] 张姣姣,郭松佳,罗琰琨. 维持性血液透析患者促红细胞生成素抵抗机制及治疗的研究进展[J]. 中国医药,2021,16(7):1108-1112. [26] 彭长坤,刘萍. 罗沙司他治疗肾性贫血的作用机制及临床研究进展[J]. 世界最新医学信息文摘,2019,19(52):89-91. [27] 张熙熙,傅雪琴,孟娇. 罗沙司他治疗维持性血液透析患者微炎症状态下贫血的疗效[J]. 中国新药与临床杂志,2021,40(9):642-645. [28] 彭思敏. 罗沙司他治疗促红素低反应性血液透析患者的疗效观察[D]. 长沙: 湖南师范大学,2021. [29] 章琴,许金华,孔祥栋,等. 罗沙司他对维持性血透患者微炎症和贫血的治疗效果[J]. 浙江中西医结合杂志,2023,33(4):318-320. doi: 10.3969/j.issn.1005-4561.2023.04.006 [30] 邹开燕. 罗沙司他治疗维持性腹膜透析促红细胞生成素低反应性贫血患者的疗效观察[D]. 广州: 广东医科大学,2022. [31] 李璐,尹忠诚,冯锦红,等. 罗沙司他代替重组人红细胞生成素治疗维持性透析患者肾性贫血的效果观察[J]. 中国血液净化,2022,21(8):564-568. doi: 10.3969/j.issn.1671-4091.2022.08.005 [32] 王曾,张阳,王琴,等. 肾性贫血并发症的研究进展[J]. 中国血液净化,2022,21(7):469-472. doi: 10.3969/j.issn.1671-4091.2022.07.002