Update of uremic toxin research by mass spectrometry

Abstract

Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on the recent progress in the MS analysis of uremic toxins. Uremic toxins include low-molecular weight solutes, protein-bound low-molecular weight solutes, and middle molecules (peptides and proteins). Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms. Notably, protein-bound uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid have emerged as important targets of therapeutic removal. Hemodialysis 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. Indoxyl sulfate is the most promising protein-bound uremic toxin as a biomarker of progress in chronic kidney disease. Novel dialysis techniques or membranes should be developed to efficiently remove these protein-bound uremic toxins for the prevention and management of uremic complications.

Correlations between Plasma Levels of Anionic Uremic Toxins and Clinical Parameters in Hemodialysis Patients

“…8 (2016) rized as UTs. 11,14,20) It is well known that the plasma levels of various UTs including IS are markedly elevated in end-stage kidney disease (ESKD) patients. 9) However, the common mechanisms underlying the elevation of their plasma levels have not yet been fully addressed.…”

“…3,13) In order to prevent such unfavorable events due to IS, it is important for clinicians and pharmacists to accurately identify plasma IS levels in HD patients. However, as highly sensitive and expensive assay equipment such as HPLC or LC/MS/MS is needed for determining plasma IS levels, 8,9,14) direct analysis of IS in a patient's plasma is not always easy in small and medium-sized medical institutions. Therefore, an easy way is required to roughly predict the plasma levels of UTs without using assay system.…”

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

“…[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.…”

Micronutrient Metabolism in Hemodialysis Patients

“…In addition to these considerations, uremic toxins include low-molecular weight solutes, medium-sized molecules (peptides and proteins), and protein-bound, low-molecular weight solutes. With regard to the latter, such as indoxyl sulfate and p-cresyl sulfate (originating from intestinal bacterial fermentation end-products of tyrosine and tryptophan), these cannot be efficiently removed by hemodialysis, even with a high-flux membrane (Niwa, 2011). Accumulation of these uremic toxins induces free radical production, and increases the expressions of transforming growth factor-β1, tissue inhibitor of metalloproteinase-1 and proalpha1(I) collagen; therefore, they play an important role in the development of cardiovascular disease and can promote the progression of renal dysfunction (Niwa, 2010).…”