p-Cresyl Sulfate

Gryp, Tessa; Vanholder, Raymond; Vaneechoutte, Mario; Glorieux, Griet

doi:10.3390/toxins9020052

Cited by 308 publications

(270 citation statements)

References 192 publications

(270 reference statements)

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“…already confirmed the colonic origin of the uremic toxins indoxyl sulfate and p‐cresol, which are being conjugated to p‐cresyl sulfate and p‐cresyl glucuronide in the liver. The cardiovascular and renal toxicity of these uremic toxins has been demonstrated in several experimental and clinical studies and concentrations of indoxyl sulfate and p‐cresyl sulfate in serum are negatively correlated with the levels of kidney function …”

Section: Gut Microbiota Composition and Metabolome In Ckdmentioning

confidence: 99%

“…Prebiotic fibers can promote the growth and activity of saccharolytic bacteria over proteolytic bacteria, and may shorten intestinal transit time, hereby lowering uremic toxic production . Indeed, prebiotics have previously been shown to reduce levels of certain colon‐derived uremic toxins in the circulation and may reduce the risk for inflammation . The provision of prebiotics during oral iron administration could therefore potentially synergyze; to reduce microbial uremic toxin production and to counteract an iron‐induced decrease in beneficial species, together contributing to reduced inflammation.…”

Section: Challenges and Alternatives For Safe Oral Iron Formulationsmentioning

confidence: 99%

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Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

Kortman

Reijnders

Swinkels

2017

Hemodialysis International

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Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota.

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Section: Gut Microbiota Composition and Metabolome In Ckdmentioning

confidence: 99%

Section: Challenges and Alternatives For Safe Oral Iron Formulationsmentioning

confidence: 99%

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

Kortman

Reijnders

Swinkels

2017

Hemodialysis International

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“…Normally excreted by the kidneys, all of these toxins exert pleiotropic toxic biological effects in CKD. For example, PCS and IS have repeatedly been associated with overall mortality, cardiovascular disease and progression of CKD [3][4][5]. Notwithstanding Shafi et al [20] failed to confirm an association between total PCS and IS and cardiovascular outcomes in prevalent HD patients in a latest post hoc analysis on the HEMO trial, a commentary in the same issue suggested that analytical issues and case-mix may explain the discrepant findings [21].…”

Section: Discussionmentioning

confidence: 95%

“…Their generation results from a sulfatation of p-cresol and indole by the enterocytes and hepatocyte, respectively, 2 solutes generated in the gut by the microbiota metabolism of tryptophan, phenylalanine and tyrosine [19]. In serum, they are both approximately 90% or more bound to Sudlow's site II of albumin and hence often as prototypes of tightly albumin-bound toxins [3][4][5]. 3-IAA, with an MW of 175 Da and a protein-binding of 70-75%, is issued from tryptophan metabolism [19].…”

Section: Discussionmentioning

confidence: 99%

Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins

et al. 2018

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Background and Objectives: While trying to optimize the dialysis clearances of protein-bound uremic toxins (PBUTs), their percentage protein binding (% PB) is an important parameter. We evaluated the effects of ionic strength, pH change and chemical displacers on the dissociation of PBUTs from albumin in vitro. Methods: PBUTs, such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresylsulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA), were spiked with human serum albumin (HSA) solution prepared with different Nacl concentrations and pH values or in the presence of a series of chemical displacers. Ultrafiltration was performed to separate the free and bound fractions, and the % PB of each PBUT was calculated. Results: For all 4 compounds, their % PB decreased with increasing ionic strength, while only slight changes occurred when the pH of the test solution increased from pH 6.0 to pH 8.5; PCS, IS and 3-IAA were relatively easily dissociated from albumin by drug displacement, while CMPF was released from HSA by all studied drugs with difficulty; the PB % for CMPF, PCS, IS and 3-IAA decreased most remarkably in the presence of free fatty acids, such as oleic acid (41.73% for CMPF, 29.9% for PCS, 23.22% for IS, and 20.34% for 3-IAA) and linoleic acid (43.12% for CMPF, 16.65% for PCS, 29.99% for IS, and 16.29% for 3-IAA). Conclusion: The protein binding of PBUTs can be decreased by higher ionic strength, increased pH and the presence of some chemical displacers, including free fatty acids. Effective dialytic removal of PBUTs may be achieved by applying these methods jointly to blood-purification techniques.

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“…p-cresol is absorbed in the gut and metabolized to pCS in enterocytes or to p-cresyl-glucuronide ( pCG ) in the liver [152,153] (Figure 3B). Although the older literature refers to increased p-cresol concentrations in CKD patients, this is an artifact generated by breakdown of pCS to p-cresol during processing for the assay.…”

Section: Nutrients As Uremic Toxins Precursors Via the Microbiotamentioning

confidence: 99%

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

et al. 2017

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In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

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p-Cresyl Sulfate

Cited by 308 publications

References 192 publications

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

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