Fu Zhangning, Geng Xiaodong, Chi Kun, Song Chengcheng, Wu Di, Liu Chao, Hong Quan
Medical School of Chinese PLA, Beijing, China.
Department of Nephrology, State Key Laboratory of Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Diseases, Beijing, China.
Front Pharmacol. 2022 Mar 10;13:746265. doi: 10.3389/fphar.2022.746265. eCollection 2022.
Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients ( < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.
达普司他是一种新型的缺氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHI），其疗效和安全性尚不清楚。因此，我们进行了这项荟萃分析，旨在研究其治疗慢性肾脏病（CKD）相关贫血患者的疗效和安全性。我们系统地检索了从数据库建立至2021年12月期间PubMed、Embase、Cochrane图书馆和临床试验注册数据库中的相关研究。我们选择了比较达普司他与重组人促红细胞生成素（rhEPO）治疗有或无透析的CKD贫血患者的随机对照试验。七项研究共7933例患者符合纳入标准。对于非透析依赖（NDD-）CKD和透析依赖（DD-）CKD患者，汇总结果显示，达普司他组和rhEPO组之间血红蛋白水平变化无显著差异（平均差（MD）=-0.01，95%置信区间（CI）=-0.38，0.35，P=0.95；MD=0.15，95%CI=-0.29，0.60，P=0.50）。此外，与rhEPO组相比，DD-CKD患者的达普司他组转铁蛋白饱和度（TSAT）、总铁结合力（TIBC）和总铁显著增加（P<0.05）。在安全性方面，DD-CKD患者中达普司他组和rhEPO组不良事件的总体发生率相似（相对危险度（RR）=0.99，95%CI=0.92，1.06，P=0.76），试验序贯分析（TSA）证实了这一结果。但对于NDD-CKD患者，达普司他组不良事件的发生率显著高于rhEPO组（RR=1.04，95%CI=1.01，1.07，P=0.02），而TSA校正了这一结果。在所有接受达普司他治疗的患者中未发现严重不良事件发生率增加的趋势，但TSA无法证实这一结果。尽管达普司他在纠正NDD-CKD和DD-CKD患者贫血方面不劣于rhEPO，但它似乎对优化DD-CKD患者的铁代谢有更好的效果。达普司他可能是治疗CKD患者贫血的一种有前景的替代药物。然而，由于纳入研究不足，未来需要进一步研究以评估达普司他的治疗效果。https://www.crd.york.ac.uk/prospero/，标识符CRD42021229636 。
