Metabolomic analysis of uremic toxins by liquid chromatography/electrospray ionization-tandem mass spectrometry

Kikuchi, Kaori; Itoh, Yoshiharu; Tateoka, Ryoko; Ezawa, Atsuko; Murakami, Kenjiro; Niwa, Toshimitsu

doi:10.1016/j.jchromb.2009.11.040

Cited by 80 publications

(58 citation statements)

References 21 publications

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“…Indoxyl sulphate was demonstrated to be the first principal serum metabolite which differentiates CKD rats from healthy rats, followed by phenyl sulphate, hippuric acid, and p- cresyl sulphate [16]. Further, we applied the metabolomic approach search for uraemic toxins as possible indicators of the effect of the oral sorbent AST-120, which absorbs uraemic toxins and/or their precursors in the intestines.…”

Section: Metabolomic Analysis Of Uraemic Toxinsmentioning

confidence: 99%

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Niwa

2013

Blood Purif

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Accumulating evidence suggests that protein-bound uraemic toxins play an important role in uraemic complications, especially in cardiovascular disease. Notably, protein-bound uraemic toxins such as indoxyl sulphate, p-cresyl sulphate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) have emerged as important targets of therapeutic removal. Indoxyl sulphate stimulates reactive oxygen species production in human umbilical vein endothelial cells (HUVEC) most intensely, followed by CMPF. Indoxyl sulphate and CMPF inhibit cell growth of HUVEC. Haemodialysis (HD) even with a high-flux membrane cannot efficiently remove the protein-bound uraemic toxins because of their high albumin-binding property. Especially, indoxyl sulphate, p-cresyl sulphate, and CMPF showed high protein-binding ratios (more than 95%) and low reduction rates by HD (less than 35%). Removal of indoxyl sulphate and p-cresyl sulphate can be improved to some extent by increasing the diffusion of the free forms with super-flux membrane HD, increasing the dialyzer mass transfer area coefficient and dialysate flow, haemodiafiltration, daily HD, and addition of a sorbent to dialysate. However, CMPF is more strongly bound to albumin (with a binding ratio of 99-100%) than indoxyl sulphate and p-cresyl sulphate, and cannot be removed at all by conventional HD. Uraemic toxins strongly or covalently bound to albumin such that CMPF can be removed by protein-leaking HD. Protein-leaking HD with a polymethylmethacrylate membrane BK-F dialyzer can reduce serum levels of CMPF with improvement of anaemia as well as reduce plasma levels of homocysteine, pentosidine, and inflammatory cytokines.

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Section: Metabolomic Analysis Of Uraemic Toxinsmentioning

confidence: 99%

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Niwa

2013

Blood Purif

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“…Metabolomics is an ideal technique for studying this syndrome, as it is quite probable that most, if not all, of the uremic toxins are actually fairly small (< 1 kD) metabolites that are well within the scope of global metabolomics. One study detected uremic toxins, indoxyl sulfate, phenyl sulfate, hippuric acid, and p-cresyl sulfate 26 and the other study found 52 metabolites increased as estimated glomerular filtration rate (eGFR) declined. 27 However, both studies did not validate specificity and pathophysiology, much less causality, of these metabolites.…”

Section: Ln and Primary Focal Segmental Glomerulosclerosis (Fsgs)mentioning

confidence: 99%

Applications of Metabolomics for Kidney Disease Research

Wettersten

Weiss

2013

Organogenesis

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Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research.

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“…High-resolution mass spectrometry has revealed the accumulation of many compounds that do not appear in lists of known metabolites and are characterized only by molecular mass. [11][12][13][14][15][16] With the inclusion of such compounds, the number of reported uremic solutes will soon rise above 500.…”

Section: The Multiplicity Of Uremic Solutesmentioning

confidence: 99%

“…Developments in mass spectrometry have made it possible to assay numerous solutes simultaneously. 11,29 The ability to assay numerous solutes has been accompanied by the development of statistical methods to relate individual solutes to clinical events. Studies combining untargeted mass spectrometry and high dimensional statistical analysis have The ratio of dialytic clearance to normal clearance is lower for other solutes, and their plasma levels therefore rise higher.…”

Section: Finding Solutes Associated With Outcomesmentioning

confidence: 99%

Approaches to Uremia

Meyer

Hostetter

2014

Journal of the American Society of Nephrology

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The development of dialysis was a dramatic step forward in medicine, allowing people who would soon have died because of lack of kidney function to remain alive for years. We have since found, however, that the "artificial kidney" does not live up fully to its name. Dialysis keeps patients alive but not well. Part of the residual illness that dialysis patients experience is caused by retained waste solutes that dialysis does not remove as well as native kidney function does. New means are available to identify these toxic solutes, about which we currently know remarkably little, and knowledge of these solutes would help us to improve therapy. This review summarizes our current knowledge of toxic solutes and highlights methods being explored to identify additional toxic solutes and to enhance the clearance of these solutes to improve patient outcomes.

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Metabolomic analysis of uremic toxins by liquid chromatography/electrospray ionization-tandem mass spectrometry

Cited by 80 publications

References 21 publications

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Applications of Metabolomics for Kidney Disease Research

Approaches to Uremia

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