Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients.

IF 1.8 4区 医学 Q3 UROLOGY & NEPHROLOGY
Ahmed A Abo Elnaga, Ibrahim Serag, Mohamed A Alsaied, Basma Badrawy Khalefa, Jaisingh Rajput, Shrouk Ramadan, Abdelrahman M Elettreby
{"title":"Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients.","authors":"Ahmed A Abo Elnaga, Ibrahim Serag, Mohamed A Alsaied, Basma Badrawy Khalefa, Jaisingh Rajput, Shrouk Ramadan, Abdelrahman M Elettreby","doi":"10.1007/s11255-024-04316-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hyperphosphatemia is common in chronic kidney disease (CKD) patients, especially patients on hemodialysis. Tenapanor is a novel drug with fewer side effects and high compliance compared to traditional phosphate binders. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of tenapanor.</p><p><strong>Methods: </strong>A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to June 25, 2024. Nine randomized controlled trials (RCTs) and three single-arm studies comparing tenapanor to placebo were included. By adopting a random-effect empirical Bayes model, STATA and RevMan were used to pool dichotomous and continuous data. The primary outcome assessed was serum phosphate. Secondary outcomes included intact parathyroid hormone (iPTH), serum calcium, potassium, and sodium, bowel movement frequency, stool consistency using BSFS score and safety outcomes.</p><p><strong>Results: </strong>Twelve studies with a total of 2,251 patients were included. Tenapanor was superior to placebo in reducing phosphate at all assessed end points, week 1 (MD = -1.28 mg/dL, P < 0.001), week 2 (MD = -1.07 mg/dL, P < 0.001), week 3 (MD = -1.22 mg/dL, P < 0.001), and week 4 (MD = -0.91 mg/dL, P < 0.001). In addition, iPTH was almost statistically significantly lower in the tenapanor group (MD = -36.53 ng/L, P = 0.07). Moreover, it led to a statistically significant reduction in sodium level (MD = -0.7 mmol/L, P = 0.0003). On the contrary, tenapanor had no statistically significant effect on calcium or potassium levels. Bowel movement frequency and stool consistency were significantly higher in the tenapanor group at all assessed end points. Regarding safety analysis, diarrhea and nausea were statistically significantly higher in the tenapanor group, (RR = 3.71, P < 0.001) and (RR = 1.97, P < 0.001), respectively. There were no significant differences in other adverse events.</p><p><strong>Conclusion: </strong>Based on our meta-analysis, tenapanor can effectively reduce serum phosphate, iPTH, and sodium. Additionally, it improves bowel movement frequency and stool consistency. However, it is associated with a higher risk of GIT symptoms that should be considered and managed during treatment. We recommend conducting further RCTs to perform head-to-head comparisons against other active comparators such as phosphate binders.</p>","PeriodicalId":14454,"journal":{"name":"International Urology and Nephrology","volume":" ","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Urology and Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11255-024-04316-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Hyperphosphatemia is common in chronic kidney disease (CKD) patients, especially patients on hemodialysis. Tenapanor is a novel drug with fewer side effects and high compliance compared to traditional phosphate binders. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of tenapanor.

Methods: A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to June 25, 2024. Nine randomized controlled trials (RCTs) and three single-arm studies comparing tenapanor to placebo were included. By adopting a random-effect empirical Bayes model, STATA and RevMan were used to pool dichotomous and continuous data. The primary outcome assessed was serum phosphate. Secondary outcomes included intact parathyroid hormone (iPTH), serum calcium, potassium, and sodium, bowel movement frequency, stool consistency using BSFS score and safety outcomes.

Results: Twelve studies with a total of 2,251 patients were included. Tenapanor was superior to placebo in reducing phosphate at all assessed end points, week 1 (MD = -1.28 mg/dL, P < 0.001), week 2 (MD = -1.07 mg/dL, P < 0.001), week 3 (MD = -1.22 mg/dL, P < 0.001), and week 4 (MD = -0.91 mg/dL, P < 0.001). In addition, iPTH was almost statistically significantly lower in the tenapanor group (MD = -36.53 ng/L, P = 0.07). Moreover, it led to a statistically significant reduction in sodium level (MD = -0.7 mmol/L, P = 0.0003). On the contrary, tenapanor had no statistically significant effect on calcium or potassium levels. Bowel movement frequency and stool consistency were significantly higher in the tenapanor group at all assessed end points. Regarding safety analysis, diarrhea and nausea were statistically significantly higher in the tenapanor group, (RR = 3.71, P < 0.001) and (RR = 1.97, P < 0.001), respectively. There were no significant differences in other adverse events.

Conclusion: Based on our meta-analysis, tenapanor can effectively reduce serum phosphate, iPTH, and sodium. Additionally, it improves bowel movement frequency and stool consistency. However, it is associated with a higher risk of GIT symptoms that should be considered and managed during treatment. We recommend conducting further RCTs to perform head-to-head comparisons against other active comparators such as phosphate binders.

替那帕诺与安慰剂治疗透析和高磷血症CKD患者的疗效和安全性:2251例患者的系统回顾和荟萃分析
背景:高磷血症在慢性肾脏疾病(CKD)患者中很常见,尤其是血液透析患者。与传统的磷酸盐结合剂相比,Tenapanor是一种副作用少、顺应性高的新型药物。我们进行了系统回顾和荟萃分析,以评估tenapanor的有效性和安全性。方法:综合检索PubMed、Scopus、Web of Science、Cochrane Library数据库,检索时间自成立至2024年6月25日。9个随机对照试验(rct)和3个单臂研究比较了tenapanor和安慰剂。采用随机效应经验贝叶斯模型,采用STATA和RevMan对二分类和连续数据进行汇总。评估的主要终点是血清磷酸盐。次要结局包括完整的甲状旁腺激素(iPTH)、血清钙、钾和钠、排便频率、粪便一致性(BSFS评分)和安全性结局。结果:12项研究共纳入2251例患者。在第1周的所有评估终点,Tenapanor在降低磷酸盐方面优于安慰剂(MD = -1.28 mg/dL, P)。结论:基于我们的荟萃分析,Tenapanor可以有效降低血清磷酸盐、iPTH和钠。此外,它改善排便频率和大便一致性。然而,它与GIT症状的高风险相关,应在治疗期间予以考虑和管理。我们建议进行进一步的随机对照试验,与其他活性比较物(如磷酸盐结合剂)进行正面比较。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
International Urology and Nephrology
International Urology and Nephrology 医学-泌尿学与肾脏学
CiteScore
3.40
自引率
5.00%
发文量
329
审稿时长
1.7 months
期刊介绍: International Urology and Nephrology publishes original papers on a broad range of topics in urology, nephrology and andrology. The journal integrates papers originating from clinical practice.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信