Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis

This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.

本研究为系统评价与荟萃分析（systematic review and meta-analysis），旨在评估罗沙司他（roxadustat）治疗慢性肾脏病（Chronic Kidney Disease, CKD）患者贫血时的心脏与肾脏相关不良反应。共纳入18项试验、总计8806名受试者用于分析。本研究采用固定效应模型（fixed-effects model）开展统计分析。
合并分析结果显示：与安慰剂组相比，接受罗沙司他治疗的CKD患者发生心脏疾病的风险无显著差异（相对风险（Relative Risk, RR）=1.049；置信区间（Confidence Interval, CI）=[0.918, 1.200]）；与促红细胞生成素类药物（Erythropoiesis-Stimulating Agents, ESA）组相比，该风险同样无显著差异（RR=1.066；CI=[0.919, 1.235]），且该结果在依赖透析（dialysis-dependent, DD）亚组（RR=1.094；CI=[0.925, 1.293]）与非依赖透析（non-dialysis-dependent, NDD）亚组（RR=1.036；CI=[0.916, 1.171]）CKD患者中均一致。
与安慰剂组（RR=1.088；CI=[0.980, 1.209]）或ESA组（RR=0.968；CI=[0.831, 1.152]）相比，罗沙司他组患者的肾脏相关不良事件发生风险亦无显著差异，该结果在DD亚组（RR=2.649；CI=[0.201, 34.981]）与NDD亚组（RR=1.053；CI=[0.965, 1.149]）中同样成立。
在依赖透析的CKD患者中，罗沙司他组患者的高钾血症发生风险存在显著差异（RR=0.939；CI=[0.898, 0.981]）。非依赖透析患者使用罗沙司他后，高血压发生率更高（RR=1.198；CI=[1.042, 1.377]）；相较于安慰剂组，该组高血压发生风险同样升高（RR=1.374；CI=[1.153, 1.638]）。
综上，无论在依赖透析还是非依赖透析的CKD患者中，罗沙司他治疗并未显著增加心脏或肾脏相关不良事件的发生风险。但需注意，依赖透析的CKD患者使用罗沙司他时需警惕高钾血症，非依赖透析患者则需关注高血压的发生。