Jia Linpei, Dong Xingtong, Yang Jingyan, Jia Rufu, Zhang Hongliang
Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Central Hospital of Cangzhou, Cangzhou 061001, China.
Ann Transl Med. 2019 Dec;7(23):720. doi: 10.21037/atm.2019.12.18.
Renal anemia is a severe complication of chronic kidney disease (CKD) and may worsen its prognosis. Roxadustat is the only oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has been proved effective to treat renal anemia. However, effects of roxadustat on non-dialysis-dependent CKD (NDD-CKD) have yet to be supported by evidence-based medicine.
Based on the databases of PubMed, EMBASE and Web of Science by 12 April 2019 (CRD42019133225), a meta-analysis of randomized controlled trials (RCTs) on roxadustat for treatment of NDD-CKD was conducted. Primary outcomes were parameters of hemoglobin (Hb) and Hb response. Secondary outcomes were hepcidin, ferritin, total iron binding capacity (TIBC), transferrin saturation (TAST), incidences of diarrhea, adverse events (AEs) and severe adverse events (SAEs). The risk of bias and the quality of evidence were assessed, respectively. Both continuous and binary variables were analyzed by the random effects models. Sensitivity analyses were performed when a significant heterogeneity was observed (P<0.1 and I>50%).
Finally, three studies with a total of 214 subjects in the roxadustat group and 80 subjects in the placebo group were enrolled. An increase of Hb [weighted mean difference (WMD) =1.22, 95% CI: 0.95 to 1.49, P<0.01], Hb response [odds ratio (OR) =27.74, 95% CI: 10.18 to 75.62, P<0.00001], and TIBC [standard mean difference (SMD) =1.59, 95% CI: 1.17 to 2.01, P<0.00001] was found. A decrease of hepcidin (SMD =-4.46, 95% CI: -5.02 to -3.89, P<0.00001), ferritin (WMD =-61.05, 95% CI: -85.70 to -36.40, P<0.00001) and TAST (WMD =-6.55, 95% CI: -8.82 to -4.29, P<0.00001) were noted as well. Analyses of incidence in diarrhea (OR =1.54, 95% CI: 0.49 to 4.79, P=0.46), AEs (OR =1.31, 95% CI: 0.76 to 2.27, P=0.34) and SAEs (OR =1.25, 95% CI: 0.29 to 5.35, P=0.76) yielded no difference between the roxadustat and the placebo groups.
Roxadustat improved renal anemia of NDD-CKD patients by improving Hb and iron metabolism. Oral administration of roxadustat was relatively safe in that roxadustat did not increase the incidence of AEs and SAEs.
肾性贫血是慢性肾脏病（CKD）的严重并发症，可能会恶化其预后。罗沙司他是唯一已被证明对治疗肾性贫血有效的口服低氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHI）。然而，罗沙司他对非透析依赖性CKD（NDD-CKD）的疗效尚未得到循证医学的支持。
基于截至2019年4月12日的PubMed、EMBASE和Web of Science数据库（CRD42019133225），对罗沙司他治疗NDD-CKD的随机对照试验（RCT）进行荟萃分析。主要结局为血红蛋白（Hb）参数和Hb反应。次要结局为铁调素、铁蛋白、总铁结合力（TIBC）、转铁蛋白饱和度（TAST）、腹泻发生率、不良事件（AE）和严重不良事件（SAE）。分别评估偏倚风险和证据质量。连续变量和二元变量均采用随机效应模型进行分析。当观察到显著异质性时（P<0.1且I>50%）进行敏感性分析。
最终，纳入三项研究，罗沙司他组共214例受试者，安慰剂组80例受试者。发现Hb升高[加权均数差（WMD）=1.22，95%CI：0.95至1.49，P<0.01]、Hb反应[比值比（OR）=27.74，95%CI：10.18至75.62，P<0.00001]和TIBC[标准均数差（SMD）=1.59，95%CI：1.17至2.01，P<0.00001]。还注意到铁调素降低（SMD =-4.46，95%CI：-5.02至-3.89，P<0.00001）、铁蛋白降低（WMD =-61.05，95%CI：-85.70至-36.40，P<0.00001）和TAST降低（WMD =-6.55，95%CI：-8.82至-4.29，P<0.00001）。腹泻发生率（OR =1.54，95%CI：0.49至4.79，P=0.46）、AE（OR =1.31，95%CI：0.76至2.27，P=0.34）和SAE（OR =1.25，95%CI：0.29至5.35，P=0.76）的分析显示罗沙司他组和安慰剂组之间无差异。
罗沙司他通过改善Hb和铁代谢改善了NDD-CKD患者的肾性贫血。口服罗沙司他相对安全，因为罗沙司他未增加AE和SAE的发生率。
