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维利美治疗慢性肾脏病所致代谢性酸中毒的疗效与安全性:一项荟萃分析。

Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis.

作者信息

Liu Wenlin, Li Lili, Zhang Xuemei, Dong Haonan, Lu Miaomiao

机构信息

Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

出版信息

Front Pharmacol. 2021 Apr 29;12:643128. doi: 10.3389/fphar.2021.643128. eCollection 2021.

DOI:10.3389/fphar.2021.643128
PMID:33995050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8117340/
Abstract

Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], < 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.

摘要

代谢性酸中毒是慢性肾脏病(CKD)的常见并发症。维美利胺是一种口服的游离胺聚合物,对胃肠道中的盐酸具有高容量和结合选择性。本研究汇总了维美利胺治疗CKD相关代谢性酸中毒的疗效和安全性的现有证据。2020年6月,我们在PubMed、Embase和Cochrane Central上对相关随机对照试验(RCT)进行了系统的文献检索。在本研究中,我们的分析纳入了三项RCT,共548例患者。分析显示,与安慰剂相比,维美利胺可使患者的碳酸氢盐水平升高(加权平均差[WMD] 3.08,95%置信区间[CI] [2.40, 3.77],P < 0.001),并通过肾脏病与生活质量简表36第3题(身体功能领域)(KDQoL-PFD)评分改善身体功能(WMD 5.25,95% CI [1.58, 8.92],P = 0.005)。对于安全性结果,两组发生头痛、腹泻、肠胃胀气和高钾血症的风险相似。总之,目前的临床证据表明,与安慰剂相比,维美利胺治疗CKD相关代谢性酸中毒有效且安全。需要进一步研究比较维美利胺长期使用与传统碱疗法的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/37fcc407ad85/fphar-12-643128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/1edaa7bb381b/fphar-12-643128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/f24cc62a561a/fphar-12-643128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/4d2b11a5c37c/fphar-12-643128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/494a5fb5bc7f/fphar-12-643128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/cfbf46b81684/fphar-12-643128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/37fcc407ad85/fphar-12-643128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/1edaa7bb381b/fphar-12-643128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/f24cc62a561a/fphar-12-643128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/4d2b11a5c37c/fphar-12-643128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/494a5fb5bc7f/fphar-12-643128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/cfbf46b81684/fphar-12-643128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/985d/8117340/37fcc407ad85/fphar-12-643128-g006.jpg

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本文引用的文献

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Veverimer for treatment of chronic metabolic acidosis in patients with chronic kidney disease.维维利美用于治疗慢性肾脏病患者的慢性代谢性酸中毒。
Ann Transl Med. 2020 Nov;8(22):1539. doi: 10.21037/atm-20-3320.
2
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J Pharmacol Exp Ther. 2020 Dec;375(3):439-450. doi: 10.1124/jpet.120.000190. Epub 2020 Oct 8.
3
Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD.
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Am J Kidney Dis. 2020 Dec;76(6):861-867. doi: 10.1053/j.ajkd.2020.07.019. Epub 2020 Sep 10.
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Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study.用碳酸氢钠治疗代谢性酸中毒会延缓慢性肾脏病的进展:UBI 研究。
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Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension.慢性肾脏病代谢性酸中毒患者使用维沃美拉的长期安全性和疗效:一项多中心、随机、双盲、安慰剂对照、40 周扩展研究。
Lancet. 2019 Aug 3;394(10196):396-406. doi: 10.1016/S0140-6736(19)31388-1. Epub 2019 Jun 24.
6
Advances in management of chronic metabolic acidosis in chronic kidney disease.慢性肾脏病中慢性代谢性酸中毒的管理进展。
Curr Opin Nephrol Hypertens. 2019 Sep;28(5):409-416. doi: 10.1097/MNH.0000000000000524.
7
Effects of Treatment of Metabolic Acidosis in CKD: A Systematic Review and Meta-Analysis.慢性肾脏病中代谢性酸中毒治疗的效果:一项系统评价与荟萃分析
Clin J Am Soc Nephrol. 2019 Jul 5;14(7):1011-1020. doi: 10.2215/CJN.13091118. Epub 2019 Jun 13.
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Metabolic Acidosis in CKD: Core Curriculum 2019.慢性肾脏病代谢性酸中毒:2019 年核心课程。
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Lancet. 2019 Apr 6;393(10179):1417-1427. doi: 10.1016/S0140-6736(18)32562-5. Epub 2019 Mar 8.