Department of Nephrology, The 1(st) Central Hospital of Tianjin, Tianjin, 300252, China.
Department of Clinical Laboratory, Occupational Disease Prevention Hospital of Tianjin, Tianjin,300021, China.
Pharmacol Res. 2020 May;155:104747. doi: 10.1016/j.phrs.2020.104747. Epub 2020 Mar 17.
The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 μmol/l (-52.2 μmol/l in NDD patients versus placebo and -7.3 μmol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 μmol/l (14.1 μmol/l in NDD patients versus placebo and 13.6 μmol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was -2.07 % (-6%, NDD patients versus placebo, and +3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.
罗沙司他（FG-4592）对接受或未接受透析的慢性肾脏病（CKD）患者的影响尚不清楚。本研究旨在评估罗沙司他治疗透析依赖（DD）或透析不依赖（NDD）CKD 患者贫血的疗效。我们对截至 2019 年 11 月的随机对照试验（RCT）进行了系统评价，比较了罗沙司他与安慰剂或促红细胞生成素α的治疗效果。我们研究了罗沙司他在 NDD 和 DD-CKD 患者肾性贫血血红蛋白水平和其他临床参数中的疗效。我们使用随机效应模型估计加权均数差（WMD）。我们纳入了 6 项 RCT，共纳入 1001 例患者，其中 70.6%接受了罗沙司他治疗，294 例为对照组。NDD-CKD 患者研究的对照组为安慰剂，而 DD-CKD 患者研究的对照组为促红细胞生成素α。中位随访时间为 8 周。所有试验均由行业资助。总体而言，罗沙司他使血红蛋白水平升高 1.20g/dl（95%CI：0.66，1.75，P<0.0001，I=99.3%）。NDD-CKD 患者血红蛋白水平升高 1.99g/dl，安慰剂组升高 0.52g/dl，DD-CKD 患者促红细胞生成素-α组升高 0.52g/dl。罗沙司他可使铁调素水平降低 49.3ng/dl（NDD 患者中-38.5ng/dl，安慰剂组和 DD 患者中-27.7ng/dl，促红细胞生成素α组），铁蛋白降低 49.7μmol/l（NDD 患者中-52.2μmol/l，安慰剂组和 DD 患者中-7.3μmol/l，促红细胞生成素α组），总铁结合力增加 32.2μmol/l（NDD 患者中 14.1μmol/l，安慰剂组和 DD 患者中 13.6μmol/l，促红细胞生成素α组）。转铁蛋白饱和度的百分比变化为-2.07%（-6%，NDD 患者，安慰剂组，DD 患者，+3.7%，促红细胞生成素α组）在贫血相关的 CKD 患者中。本综述发现罗沙司他可增加 NDD 和 DD-CKD 患者的血红蛋白、血清转铁蛋白、肠道铁吸收水平，并降低铁调素水平。安全性数据仍在不断涌现。
