Liu Chao, Fu Zhangning, Jiang Jiawei, Chi Kun, Geng Xiaodong, Mao Zhi, Song Chengcheng, Sun Guannan, Hong Quan, Cai Guangyan, Chen Xiangmei, Sun Xuefeng
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Department of Critical Care Medicine, Tianjin Medical University First Center Clinical College, Tianjin, China.
Front Med (Lausanne). 2021 Aug 31;8:724456. doi: 10.3389/fmed.2021.724456. eCollection 2021.
Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial. The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis. Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat. Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.
罗沙司他是一种缺氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHI），已被用于治疗慢性肾脏病（CKD）患者的贫血。然而，其安全性和有效性仍存在争议。检索了PubMed、EMBASE、科学引文索引、Cochrane对照试验中央注册库和临床试验注册库数据库，以查找截至2021年4月发表的相关研究。我们纳入了比较罗沙司他与安慰剂或促红细胞生成剂（ESA）用于有或无透析的CKD贫血患者的随机对照试验（RCT）。11项研究共6631例患者符合纳入标准。在非透析依赖（NDD-）和透析依赖（DD-）的CKD患者中，罗沙司他组和对照组（NDD-CKD患者为安慰剂，DD-CKD患者为ESA）的总不良事件无显著差异[相对风险（RR）=1.02，95%置信区间（CI）=1.00,1.04，P=0.08；RR=1.22，95%CI=0.91,1.64，P=0.18]，试验序贯分析（TSA）在NDD-CKD组中证实了该结果。在DD-CKD组中，罗沙司他与安慰剂之间的高钾血症和感染发生率无显著差异。汇总结果显示，与安慰剂相比，罗沙司他在NDD-CKD组中显著提高了血红蛋白反应率，在DD-CKD组中的效果与ESA相似。然而，罗沙司他似乎并未明显优化铁代谢参数。罗沙司他可安全用于CKD患者。口服罗沙司他作为NDD-CKD患者贫血治疗药物比安慰剂更有效，在纠正DD-CKD患者贫血方面不劣于ESA。然而，仍需要更多临床试验来进一步证明罗沙司他是否能优化铁代谢。
