Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD

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. Phenylac...

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Published in:Journal of the American Society of Nephrology 2016-11, Vol.27 (11), p.3479-3487
Main Authors: Poesen, Ruben, Claes, Kathleen, Evenepoel, Pieter, de Loor, Henriette, Augustijns, Patrick, Kuypers, Dirk, Meijers, Björn
Format: Article
Language:English
Subjects:
Adult
Aged
Cardiovascular Diseases - etiology
Clinical Research
Female
Glutamine - analogs & derivatives
Glutamine - blood
Humans
Male
Microbiota
Middle Aged
Prospective Studies
Renal Insufficiency, Chronic - blood
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - microbiology
Renal Insufficiency, Chronic - mortality
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Summary: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
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2015121302