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非奈利酮治疗慢性肾脏病的疗效与安全性:一项随机临床试验的系统评价和荟萃分析

Efficacy and Safety of Finerenone in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

作者信息

Zhang Ming-Zhu, Bao Wujisiguleng, Zheng Qi-Yan, Wang Ya-Hui, Sun Lu-Ying

机构信息

Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Pharmacol. 2022 Feb 7;13:819327. doi: 10.3389/fphar.2022.819327. eCollection 2022.

Abstract

Chronic kidney disease (CKD) is a global public health issue. In recent years, the effectiveness of finerenone for treatment of CKD has been the subject of considerable debate. The main objective of the current meta-analysis was to validate the clinical efficacy and safety of finerenone in patients with CKD. Seven databases were searched for randomized controlled trials (RCTs) comparing finerenone with placebo in patients with CKD. Data from eligible studies were extracted, and the Cochrane risk of bias tool utilized for evaluating the methodological quality of RCTs. The effect size was estimated using the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). Five trials (n = 13,078) were included. Compared to placebo groups, the urinary albumin-to-creatinine ratio (UACR) mean from the baseline was significantly lower [MD -0.30 (95% CI -0.32, -0.28), < 0.00001], while a decrease in the estimated glomerular filtration rate (eGFR) from baseline was significantly higher [MD -2.44 (95% CI -2.82, -2.05), < 0.00001] for the finerenone groups. Furthermore, the proportion of patients with decreased eGFR (≥40%) post-baseline was significantly lower [RR 0.85 (95% CI 0.78, 0.93), = 0.0002], along with end-stage kidney disease (ESKD) [RR 0.80 (95% CI 0.65, 0.99), = 0.04] and cardiovascular events (CVs) [RR 0.88 (95% CI 0.80, 0.95), < 0.003] in the finerenone groups. In terms of safety, the increase in the serum potassium concentration and incidence of hyperkalemia was significantly higher for the finerenone groups [MD 0.17 (95% CI 0.10, 0.24), < 0.00001; RR 2.03 (95% CI 1.83, 2.26), < 0.00001, respectively], but the incidence of adverse events (AEs) was similar to placebo [RR 1.00 (95% CI 0.98-1.01), = 0.67]. In all cases, the results were rated as providing moderate-quality or high-quality evidence. Data from our meta-analysis suggest that finerenone confers significant renal and cardiovascular benefits in patients with CKD. While higher risk of hyperkalemia was observed with finerenone than placebo, differences in AEs were not significant. Finerenone may therefore present a novel promising therapeutic agent for patients with CKD. : [https://inplasy.com/inplasy-2021-9-0020/], identifier [INPLASY202190020].

摘要

慢性肾脏病(CKD)是一个全球性的公共卫生问题。近年来,非奈利酮治疗CKD的有效性一直是相当多争论的主题。当前这项荟萃分析的主要目的是验证非奈利酮在CKD患者中的临床疗效和安全性。检索了七个数据库以查找比较非奈利酮与安慰剂治疗CKD患者的随机对照试验(RCT)。提取符合条件研究的数据,并使用Cochrane偏倚风险工具评估RCT的方法学质量。使用风险比(RR)和平均差(MD)及95%置信区间(CI)估计效应量。纳入了五项试验(n = 13,078)。与安慰剂组相比,非奈利酮组从基线开始的尿白蛋白与肌酐比值(UACR)均值显著更低[MD -0.30(95%CI -0.32,-0.28),<0.00001],而从基线开始的估计肾小球滤过率(eGFR)下降显著更高[MD -2.44(95%CI -2.82,-2.05),<0.00001]。此外,非奈利酮组基线后eGFR下降(≥40%)的患者比例显著更低[RR 0.85(95%CI 0.78,0.93),=0.0002],以及终末期肾病(ESKD)[RR 0.8(95%CI 0.65,0.99),=0.04]和心血管事件(CV)[RR 0.88(95%CI 0.80,0.95),<0.003]。在安全性方面 [https://inplasy.com/inplasy-2021-9-0020/],非奈利酮组血清钾浓度升高和高钾血症发生率显著更高[MD 0.17(95%CI 0.10,0.24),<0.00001;RR 2.03(95%CI 1.83,2.26),<0.00001],但不良事件(AE)发生率与安慰剂相似[RR 1.00(95%CI 0.98 - 1.01),=0.67]。在所有情况下,结果被评为提供中等质量或高质量证据。我们荟萃分析的数据表明,非奈利酮在CKD患者中具有显著的肾脏和心血管益处。虽然观察到非奈利酮导致高钾血症的风险高于安慰剂,但AE差异不显著。因此,非奈利酮可能是一种对CKD患者有前景的新型治疗药物。标识符[INPLASY202190020] 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5980/8859447/21dd64df0383/fphar-13-819327-g001.jpg

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