title: Correlation between Serum Levels of Protein-Bound Uremic Toxins in Hemodialysis Patients Measured by LC/MS/MS.
abstract: 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.
authors.affiliation: Biomedical Research Laboratories, Kureha Corporation.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Biomedical Research Laboratories, Kureha Corporation.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ezawa
authors.affiliation: Biomedical Research Laboratories, Kureha Corporation.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Meiyo Clinic.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tsuruta
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
keywords: indoxyl glucuronide; indoxyl sulfate; p-cresyl glucuronide; p-cresyl sulfate; phenyl sulfate; phenylacetylglutamine