Abstract
If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden.
Highlights
IntroductionA myriad of compounds, the so-called uremic retention solutes, accumulate in the circulation and tissues [1,2,3]
When kidney function deteriorates, a myriad of compounds, the so-called uremic retention solutes, accumulate in the circulation and tissues [1,2,3]
The gut microbiota plays an important role in human health and disease [16,17], with alterations of the intestinal microbiota linked to the development of different diseases, such as inflammatory bowel disease [18], cancer [19], obesity [20], diabetes [21,22], cardiovascular disease [23], and kidney disease [24]
Summary
A myriad of compounds, the so-called uremic retention solutes, accumulate in the circulation and tissues [1,2,3]. To the small water-soluble compounds (500 Da) the protein-bound compounds form a third group. Many of these compounds, amongst which the phenols and indoles, originate from the intestinal microbial metabolism of dietary amino acids [8]. Whereas in the healthy kidney, removal of protein-bound solutes largely depends on tubular secretion, removal by dialysis, primarily replacing the filtration capacity of the kidney, is limited to the unbound fraction and is not affected by dialyzer pore size [9], and only marginally by convection [10]. For the protein-bound compounds alternative measures, preferably preventive (such as decreasing generation, adsorption, and preserving kidney function), will be necessary to keep concentrations low. We will especially focus on the intestinal origin of pCS and the contributing bacterial species which could be a future target to decrease levels and toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
