替那帕诺治疗透析合并高磷血症患者的有效性及安全性:基于随机、安慰剂对照的Meta分析

Effects and safety of Tenapanor in hemodialysis patients with hyperphosphatemia:a meta-analysis of randomized placebo-controlled trials

目的对替那帕诺(Tenapanor)的随机对照试验进行荟萃分析,以研究替那帕诺对透析合并高磷血症患者的降磷效果。方法检索The Cochrane Library、PubMed、Embase、Web of Science和中国知网、万方、维普等数据库,搜索替那帕诺治疗透析合并高磷血症患者相关的随机、对照研究;主要终点为血清磷相对于基线的变化(mean difference,MD),次要终点为目标值(血清磷<6mg/dl)的率差(rate difference,RD);对试验时试验组是否伴有磷酸盐结合剂进行亚组分析;收集药物相关不良反应及腹泻相关资料以判断替那帕诺的安全性。结果共4项符合条件的研究,677名患者。研究结果表明替那帕诺对透析合并高磷血症患者的降磷效果显著。血清磷水平降低了2.345mg/dl(95%CI:-2.798~-1.892;P<0.001),试验组患者达到血清磷<6mg/dl目标值的比率高于安慰剂组(RD=0.363;95%CI:0.147~0.579;P<0.001)。替那帕诺组总药物相关不良反应率(RD=0.461;95%CI:0.284~0.637;P<0.001)及腹泻发生率(RD=0.429;95%CI:0.354~0.505;P<0.001)均高于安慰剂组。亚组分析结果显示试验组单独使用替那帕诺(MD=-2.468;95%CI:-3.013~-1.923;P<0.001)或者使用替那帕诺联合磷酸盐结合剂(MD=-2.070;95%CI:-2.885~-1.255;P<0.001)均能降低血清磷水平。结论无论是否联合使用磷酸盐结合剂,替那帕诺均可降低透析合并高磷血症患者的血磷水平;但不良反应发生率较高,主要表现为腹泻。

Objective To evaluate the effects and safety of Tenapanor in hemodialysis patients with hyperphosphatemia by an updated meta-analysis.Methods All randomized controlled trials of Tenapanor were systematically searched in the Cochrane Library,PubMed,Embase,Web of Science,CNKI,Wan fang and VIP databases.The primary endpoint was the mean difference(MD)of serum phosphorus changes using Tenapanor versus placebo control,and the secondary endpoint was the rate difference(RD)of the target serum phosphorus level(serum phosphorus level:≤6 mg/dl).A subgroup analysis was also conducted based on whether phosphate binders were used.Drug-related adverse reactions and diarrhea were collected to determine the safety of Tenapanor.Results There were 4 eligible trials that enrolled 677 patients.The studies showed that Tenapanor significantly reduced serum phosphorus level by 2.345mg/dl(95%CI:-2.798~-1.892;P<0.001)and the achievement of the target serum phosphorus level(RD=0.363;95%CI:0.147~0.579;P<0.001)was better than placebo.However,drug-related adverse events(RD=0.461;95%CI:0.284~0.637;P<0.001),and diarrhea(RD=0.429;95%CI:0.354~0.505;P<0.001)were more serious than placebo.Subgroup analysis found that there were no significant differences in the magnitude of serum phosphorus level with(MD=-2.070;95%CI:-2.885~-1.255;P<0.001)or without(MD=-2.468;95%CI:-3.013~-1.923;P<0.001)phosphate binders.Conclusions The randomized placebo-controlled trials showed that Tenapanor significantly reduced serum phosphorus level in hemodialysis patients with hyperphosphatemia with or without use of phosphate binders.Diarrhea was present frequently but no serious drug-related adverse events occurred.