这项研究比较了使用罗沙司他与促红细胞生成素刺激剂(ESA)治疗的贫血慢性肾病患者的心血管风险。它还探讨了Roxadustat对心血管的影响。
■我们搜索了PubMed,EMBASE,科克伦,Scopus,和截至2023年8月13日的WebofScience数据库,使用诸如“ESA,\"\"Roxadustat,\"\"MACE,\"\"笔画,\"\"死亡,心肌梗塞,“和”心力衰竭。“两名研究人员根据预定义的标准独立选择和提取数据。我们使用Cochrane工具评估偏倚风险,并使用Q和I2检验分析统计异质性。我们按地理区域进行了亚组分析,并使用Stata14.0和RevMan5.4软件进行了数据分析。数据来自NCBI数据库,通过过滤“Roxadustat”和“human”,并使用R软件鉴定差异表达基因,将显著性设置为p<0.01和2倍logFC,其次是GO富集分析,KEGG通路分析,和蛋白质相互作用网络分析。
■共分析了15篇文章,其中包括1,43,065名患者,包括1,38,739例接受ESA治疗的患者和4,326例接受Roxadustat治疗的患者。在总体人口荟萃分析中,主要不良心血管事件(MACE)的发生率,死亡,心力衰竭(HF)占13%,8%,在Roxadustat组中为4%,与17%相比,12%,欧空局组有6%,分别,P值大于0.05。在亚组分析中,发病率为13%,11%,Roxadustat组为4%,而17%,15%,欧空局集团为5%,p值也大于0.05。生物信息学分析确定了59个差异表达基因,主要参与炎症反应。GO富集分析揭示这些基因主要与整联蛋白结合有关。确定的主要途径是TNF信号通路,NF-κB信号通路,和脂质代谢与动脉粥样硬化有关。蛋白质相互作用网络突出了IL1B,CXCL8、ICAM1、CCL2和CCL5作为前五个显著差别的基因,所有这些都参与了炎症反应,并被Roxadustat下调,提示在减少炎症方面的潜在作用。
■荟萃分析表明,使用Roxadustat和ESA治疗与慢性肾脏疾病相关的贫血不会显着改变整体和美国人群中心血管事件的可能性。然而,Roxadustat在MACE方面表现出更安全的形象,死亡,和心力衰竭。生物信息学发现表明,Roxadustat可能影响整合素粘附并影响TNF和NF-κB信号通路,随着脂质和动脉粥样硬化途径,有可能减少炎症。
UNASSIGNED: This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat.
UNASSIGNED: We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as \"ESA,\" \"Roxadustat,\" \"MACE,\" \"stroke,\" \"death,\" \"myocardial infarction,\" and \"heart failure.\" Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for \"Roxadustat\" and \"human,\" and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis.
UNASSIGNED: A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation.
UNASSIGNED: The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.