Recent progress in the analysis of uremic toxins by mass spectrometry

Niwa, Toshimitsu

doi:10.1016/j.jchromb.2008.11.032

Cited by 38 publications

(19 citation statements)

References 58 publications

(49 reference statements)

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“…Interrogation of the metabolome potentially offers unprecedented insights into a disease or phenotype and provides initial access to biomarker and pathway discovery [7][8][9]. We applied these improved techniques to probe the metabolomes of Chinese type 2 diabetic patients with low eGFR.…”

Section: Introductionmentioning

confidence: 99%

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

Salim

Liu

et al. 2011

Diabetologia

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Aims/hypothesis We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes. Methods Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n=44) with low eGFR and controls (n=46) had eGFR values <60 and ≥60 ml min , respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/ MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression. Results Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value=2.62×10

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Section: Introductionmentioning

confidence: 99%

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

Salim

Liu

et al. 2011

Diabetologia

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“…AST-120, a potent activated charcoal preparation has been shown to decrease the plasma concentration of p-cresol sulfate and indoxyl sulfate, 54,55 which are among the uremic toxins originating from p-cresol and indole generated by the colonic microbial flora. 3,56,57 In addition, AST-120 administration in animal models of CKD attenuates inflammation and oxidative stress and slows the progression of renal disease. [58][59][60] The beneficial effects of AST-120 primarily have been attributed to its ability to reduce production and absorption of p-cresol sulfate and indoxyl sulfate.…”

Section: In the Stools And Gastrointestinal Tractmentioning

confidence: 99%

Gases as Uremic Toxins: Is There Something in the Air?

Jankowski

Westhof

Vaziri

et al. 2014

Seminars in Nephrology

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Summary: The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example, protein-binding, dimensions, and so forth. The endogenous compounds of a gaseous nature have received much attention lately from the scientific community because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds are phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid and phenyl acetic acid, trimethylamine, and dimethylamine; among the inorganic solutes are ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this article, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools, and the gastrointestinal tract. In addition, the effect of the dialysis procedure on exhaled gases are described. Semin Nephrol 34:135-150 C 2014 Published by Elsevier Inc.

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“…[6][7][8] Based on MS analysis of uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms. LC/MS with electrospray ionization (ESI) can separate and identify highly polar, thermally labile and/or high-molecular weight mixture compounds.…”

Section: Analysis Of Uremic Toxins With Liquid Chromatography/mass Spmentioning

confidence: 99%

Correlation between Serum Levels of Protein-Bound Uremic Toxins in Hemodialysis Patients Measured by LC/MS/MS

et al. 2013

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Uremic toxins are involved in a variety of symptoms in advanced chronic kidney disease. Especially, the accumulation of protein-bound uremic toxins in the blood of dialysis patients might play an important role in the development of cardiovascular disease. Serum concentration of protein-bound uremic toxins such as indoxyl sulfate, indoxyl glucuronide, indoleacetic acid, p-cresyl sulfate, p-cresyl glucuronide, phenyl sulfate, phenyl glucuronide, phenylacetic acid, phenylacetylglutamine, hippuric acid, 4-ethylphenyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) in hemodialysis patients were simultaneously measured by liquid chromatography/tandem mass spectrometry. Serum levels of these protein-bound uremic toxins were increased in hemodialysis patients. Indoxyl sulfate, p-cresyl sulfate, and CMPF could not be removed efficiently by hemodialysis due to their high protein-binding ratios. Serum level of total indoxyl sulfate did not show any significant correlation with total p-cresyl sulfate. However, free indoxyl sulfate correlated with free p-cresyl sulfate, and reduction rate by hemodialysis of indoxyl sulfate correlated with that of p-cresyl sulfate. Serum levels of total and free indoxyl sulfate showed significantly positive correlation with those of indoxyl glucuronide, phenyl sulfate, and phenyl glucuronide. Serum levels of total and free p-cresyl sulfate showed significantly positive correlation with those of p-cresyl glucuronide, phenylacetylglutamine, and phenylacetic acid. Indoxyl sulfate and indoxyl glucuronide are produced from indole which is produced in the intestine from tryptophan by intestinal bacteria. p-Cresyl sulfate and p-cresyl glucuronide are produced from p-cresol which is produced in the intestine from tyrosine by intestinal bacteria. Thus, intestinal bacteria play an important role in the metabolism of protein-bound uremic toxins.Keywords: indoxyl sulfate, indoxyl glucuronide, phenyl sulfate, p-cresyl sulfate, p-cresyl glucuronide, phenylacetylglutamine (Received July 30, 2012; Accepted November 5, 2012) UREMIC TOXINSUremic toxins are involved in a variety of symptoms in patients with stage-5 chronic kidney disease (CKD). More than ninety compounds have been considered to be uremic toxins.1) Uremic toxins include: 1) free water-soluble lowmolecular-weight solutes with molecular weight less than 500 such as urea, 2) protein-bound solutes such as indoxyl sulfate, and 3) middle molecules with molecular weight more than 500 such as β2-microglobulin.1) Notably, proteinbound uremic toxins such as indoxyl sulfate and p-cresyl sulfate have emerged as important targets of therapeutic removal. Hemodialysis (HD) even with a high-flux membrane cannot efficiently remove the protein-bound uremic toxins because of their high albumin-binding property. The accumulation of these protein-bound uremic toxins in the blood of dialysis patients might play an important role in the development of uremic complications such as cardiovascular disease (CVD). Indoxyl sulfate is the most prom...

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Recent progress in the analysis of uremic toxins by mass spectrometry

Cited by 38 publications

References 58 publications

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

Gases as Uremic Toxins: Is There Something in the Air?

Correlation between Serum Levels of Protein-Bound Uremic Toxins in Hemodialysis Patients Measured by LC/MS/MS

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