Wang Lijun, Yin Heng, Yang Liling, Zhang Fenglian, Wang Song, Liao Dan
Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
Front Pharmacol. 2022 Apr 26;13:779694. doi: 10.3389/fphar.2022.779694. eCollection 2022.
Chronic kidney disease (CKD) is a global public health problem, and anemia is a common complication in CKD patients. Roxadustat (FG-4592) is an oral hypoxia-inducible factor (HIF) stabilizer. Roxadustat has been shown in studies to keep up with and increase hemoglobin better than placebo or erythropoietin. The purpose of this meta-analysis was to assess the efficacy and safety of roxadustat. We searched CBM, CNKI, VIP, Wanfang Database, PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials of roxadustat for the treatment of anemia in CKD patients. The papers were screened using rigorous criteria and their quality was assessed using the Cochrane 5.1.0 assessment manual for randomized controlled trials (RCTs). RevMan 5.3 was used to extract and synthesize data for meta-analysis. There were 8 RCTs (7 articles) in all, and 1,364 patients with chronic kidney disease anemia were involved. The overall quality of the studies included was satisfactory. The meta-analysis findings revealed that roxadustat can considerably enhance hemoglobin, transferrin, and total iron binding capacity (TIBC) in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients: Hemoglobin (Hb): DD: [SMD = 0.23, 95% CI (0.01, 0.44), = 0.04], NDD: [SMD = 2.08, 95% CI (1.23, 2.93) < 0.000001]; transferrin: DD: [SMD = 0.78, 95% CI (0.24, 1.32), = 0.004], NDD: [SMD = 1.37, 95% CI (0.76, 1.98), < 0.0001]; TIBC: DD [SMD = 0.97, 95% CI (0.64, 1.29), < 0.00001], NDD [SMD = 1.34, 95% CI (0.9, 1.78), < 0.00001]. After roxadustat therapy, patients' serum iron levels were considerably higher in the dialysis group than in the control group, but there was no significant change in the NDD group [SMD = 0.42, 95% CI (0.27, 0.57), < 0.00001]. In the NDD group, hepcidin, ferritin, and transferrin saturation (TSAT) were significantly reduced after roxadustat treatment: Hepcidin [SMD = -1.59, 95% CI (-2.69, -0.49), = 0.005], ferritin [SMD = -0.51, 95% CI (-0.72, 0.3) < 0.00001], TSAT [SMD = -0.41, 95% CI (-0.62, 0.2), < 0.0001]. In terms of safety, adverse events (AE) [SMD = 1.08, 95% CI (0.98, 1.18) = 0.11] and serious adverse events (SAE) [SMD = 1.32, 95% CI (0.97, 1.9) = 0.08] were not significantly different between the two groups. Roxadustat can improve anemia in NDD patients with chronic kidney disease, and its short-term safety was comparable to that of the comparison group.
慢性肾脏病（CKD）是一个全球性的公共卫生问题，贫血是CKD患者常见的并发症。罗沙司他（FG-4592）是一种口服的缺氧诱导因子（HIF）稳定剂。研究表明，罗沙司他在提高血红蛋白水平方面优于安慰剂或促红细胞生成素。本荟萃分析的目的是评估罗沙司他的疗效和安全性。我们检索了中国生物医学文献数据库（CBM）、中国知网（CNKI）、维普资讯（VIP）、万方数据库、PubMed、Cochrane图书馆、Embase和Web of Science，以查找罗沙司他治疗CKD患者贫血的随机对照试验。使用严格的标准筛选文献，并使用Cochrane 5.1.0随机对照试验（RCT）评估手册评估其质量。使用RevMan 5.3提取和综合数据进行荟萃分析。共有8项RCT（7篇文章），涉及1364例慢性肾脏病贫血患者。纳入研究的总体质量令人满意。荟萃分析结果显示，罗沙司他可显著提高依赖透析（DD）和非依赖透析（NDD）患者的血红蛋白、转铁蛋白和总铁结合力（TIBC）：血红蛋白（Hb）：DD：[标准化均数差（SMD）=0.23，95%置信区间（CI）（0.01，0.44），P=0.04]，NDD：[SMD=2.08，95%CI（1.23，2.93），P<0.000001]；转铁蛋白：DD：[SMD=0.78，95%CI（0.24，1.32），P=0.004]，NDD：[SMD=1.37，95%CI（0.76，1.98），P<0.0001]；TIBC：DD[SMD=0.97，95%CI（0.64，1.29），P<0.00001]，NDD[SMD=1.34，95%CI（0.9，1.78），P<0.00001]。罗沙司他治疗后，透析组患者的血清铁水平显著高于对照组，但NDD组无显著变化[SMD=0.42，95%CI（0.27，0.57），P<0.00001]。在NDD组中，罗沙司他治疗后铁调素、铁蛋白和转铁蛋白饱和度（TSAT）显著降低：铁调素[SMD=-1.59，95%CI（-2.69，-0.49），P=0.005]，铁蛋白[SMD=-0.51，95%CI（-0.72，-0.3），P<0.00001]，TSAT[SMD=-0.41，95%CI（-0.62，-0.2），P<0.0001]。在安全性方面，两组之间的不良事件（AE）[SMD=1.08，95%CI（0.98，1.18），P=0.11]和严重不良事件（SAE）[SMD=1.32，95%CI（0.97，1.9），P=0.08]无显著差异。罗沙司他可改善NDD慢性肾脏病患者的贫血，其短期安全性与对照组相当。
