Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD
Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD
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DOI：
10.1681/asn.2015121302
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发表时间：
2016-11-01
影响因子：
13.6
通讯作者：
Meijers, Bjorn
中科院分区：
文献类型：
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作者：
Poesen, Ruben;Claes, Kathleen;Meijers, Bjorn
结肠微生物代谢实质上有助于尿毒症溶质的产生。对甲苯基硫酸盐和吲哚基硫酸盐是微生物来源的溶质的主要代表，也是蛋白质结合的溶质，表现出高蛋白质结合亲和力和对肾小管分泌的依赖性。苯乙酰谷氨酰胺是另一种高度依赖于肾小管分泌但低蛋白结合亲和力的微生物代谢产物。这些溶质的相关性尚不清楚。因此，我们前瞻性地随访了488例CKD 1-5期患者，并通过液相色谱-质谱法测定了血清苯乙酰谷氨酰胺。在一个亚组中，我们确定了24小时尿排泄作为苯乙酰谷氨酰胺肠吸收以及肾清除率的替代。我们对死亡率（51例事件）和心血管疾病（75例事件）进行了结局分析。血清苯乙酰谷氨酰胺水平与24小时尿排泄量相关（rho=0.55; P
Colonic microbial metabolism substantially contributes to uremic solute production. p-Cresyl sulfate and indoxyl sulfate are the main representatives of solutes of microbial origin and also, protein-bound solutes, exhibiting high protein-binding affinity and dependence on tubular secretion. Phenylacetylglutamine is another microbial metabolite with high dependence on tubular secretion but low protein-binding affinity. The relevance of such solutes is unknown. Therefore, we prospectively followed 488 patients with CKD stages 1-5 and a measurement of serum phenylacetylglutamine by liquid chromatography-mass spectrometry. In a subgroup, we determined 24-hour urinary excretion as a surrogate of intestinal uptake as well as renal clearance of phenylacetylglutamine. We performed outcome analysis for mortality (51 events) and cardiovascular disease (75 events). Serum phenylacetylglutamine level correlated with 24-hour urinary excretion (rho=0.55; P