Abo Elnaga Ahmed A, Serag Ibrahim, Alsaied Mohamed A, Khalefa Basma Badrawy, Rajput Jaisingh, Ramadan Shrouk, Elettreby Abdelrahman M
Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Int Urol Nephrol. 2025 Jun;57(6):1835-1850. doi: 10.1007/s11255-024-04316-x. Epub 2024 Dec 19.
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.
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.
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.
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.
高磷血症在慢性肾脏病（CKD）患者中很常见，尤其是接受血液透析的患者。与传统的磷结合剂相比，替那帕诺是一种副作用较少且依从性高的新型药物。我们进行了一项系统评价和荟萃分析，以评估替那帕诺的疗效和安全性。
对PubMed、Scopus、Web of Science和Cochrane图书馆进行了全面检索，检索时间从建库至2024年6月25日。纳入了9项随机对照试验（RCT）和3项比较替那帕诺与安慰剂的单臂研究。采用随机效应经验贝叶斯模型，使用STATA和RevMan对二分法和连续数据进行汇总。评估的主要结局是血清磷。次要结局包括完整甲状旁腺激素（iPTH）、血清钙、钾和钠、排便频率、使用布里斯托大便性状评分（BSFS）评估的大便性状以及安全性结局。
共纳入12项研究，总计2251例患者。在所有评估的终点，即第1周（MD = -1.28mg/dL，P < 0.001）、第2周（MD = -1.07mg/dL，P < 0.001）、第3周（MD = -1.22mg/dL，P < 0.001）和第4周（MD = -0.91mg/dL，P < 0.001），替那帕诺在降低磷方面优于安慰剂。此外，替那帕诺组的iPTH几乎在统计学上显著降低（MD = -36.53ng/L，P = 0.07）。而且，它导致钠水平在统计学上显著降低（MD = -0.7mmol/L，P = 0.0003）。相反，替那帕诺对钙或钾水平没有统计学上的显著影响。在所有评估的终点，替那帕诺组的排便频率和大便性状均显著更高。关于安全性分析，替那帕诺组的腹泻和恶心在统计学上显著更高，分别为（RR = 3.71，P < 0.001）和（RR = 1.97，P < 0.001）。其他不良事件没有显著差异。
基于我们的荟萃分析，替那帕诺可有效降低血清磷、iPTH和钠。此外，它可改善排便频率和大便性状。然而，它与胃肠道症状的较高风险相关，在治疗期间应予以考虑和处理。我们建议进行进一步的随机对照试验，以与其他活性对照药物如磷结合剂进行直接比较。
