Beijing University of Chinese Medicine, Beijing, 100029, China; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Beijing, 100700, China.
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Pharmacol Res. 2020 Sep;159:105020. doi: 10.1016/j.phrs.2020.105020. Epub 2020 Jun 16.
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95 % confidence interval [CI]: ‒0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95 % CI: 0.93-3.99) for desidustat, 1.81 (0.87-2.75) for enarodustat, 1.68 (0.64-2.72) for molidustat, 1.66 (0.89-2.44) for epoetin, 1.63 (0.69-2.56) for darbepoetin, 1.61 (0.99-2.22) for roxadustat, and 1.55 (0.74-2.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95 % CI, 0.06-2.59]; roxadustat, 0.40 (0.06-2.84); enarodustat, 0.33 (0.01-16.25); desidustat, 0.34 (0.01-17.00); epoetin, 0.50 (0.18-1.42); daprodustat, 0.54 (0.09-3.31); darbepoetin, 1.03 (0.65-1.65); and vadadustat, 1.43 (0.15-13.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.
缺氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHIs）是一类新的口服药物，正在开发用于治疗慢性肾脏病（CKD）患者的贫血。本研究旨在比较 HIF-PHI 与促红细胞生成素和达贝泊汀在未接受透析的 CKD 贫血患者中的疗效和安全性。从建库到 2019 年 10 月，检索了 PubMed、Embase、Cochrane 图书馆、Web of Science 和 clinicaltrials.gov 数据库，以调查用于治疗未接受透析的 CKD 贫血患者的不同药物（6 种 HIF-PHIs、促红细胞生成素、达贝泊汀和安慰剂）的随机对照试验。主要结局包括血红蛋白（Hb）水平变化和全因死亡率。共纳入 19 项研究。与安慰剂相比，除vadadustat（平均差异：1.12，95%置信区间[CI]：-0.11-2.35）外，其他药物均显著升高 Hb 水平，desidustat 为 2.46（95%CI：0.93-3.99），enarodustat 为 1.81（0.87-2.75），molidustat 为 1.68（0.64-2.72），促红细胞生成素为 1.66（0.89-2.44），达贝泊汀为 1.63（0.69-2.56），roxadustat 为 1.61（0.99-2.22），daprodustat 为 1.55（0.74-2.36）。在这 8 种药物中，Hb 水平升高无显著差异。与安慰剂相比，药物与全因死亡率之间也无显著相关性（molidustat 的 RR 为 0.39[95%CI，0.06-2.59]；roxadustat 为 0.40[95%CI，0.06-2.84]；enarodustat 为 0.33[95%CI，0.01-16.25]；desidustat 为 0.34[95%CI，0.01-17.00]；促红细胞生成素为 0.50[95%CI，0.18-1.42]；daprodustat 为 0.54[95%CI，0.09-3.31]；达贝泊汀为 1.03[95%CI，0.65-1.65]；vadadustat 为 1.43[95%CI，0.15-13.27]）。在这些药物中，全因死亡率无显著差异。总之，这些 HIF-PHIs 对治疗未接受透析的 CKD 贫血患者有效且相对耐受。进一步的研究应考虑到我们研究的局限性，以评估这些 HIF-PHIs 在临床环境中的价值。
