The Functional Analysis of Uremic Toxins by Metabolomics

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 12968

Special Issue Editors

Tohoku University | Division of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Sendai, Japan
Interests: uremic toxins; metabolomic analysis; uremic toxins-related organ damage; indoxyl sulphate
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Guest Editor
Tohoku University | Department of Integrative Genomics, Tohoku Medical Megabank Organization, Sendai, Japan
Interests: liquid chromatography mass spectrometry, mass spectrometry imaging, metabolomics, lipidomics, microbiome, biomarker searching for kidney diseases

Special Issue Information

Dear Colleagues,

Metabolomic analysis is the comprehensive analysis of small molecules within the body. These small molecules are known as metabolites, and reflect the underlying biochemical activity and state of cells or tissues. Thus, metabolomic analysis using mass spectrometry is a powerful tool to capture disease-metabolic signatures, and widely used for biomarker discovery and understanding of pathogenesis.

Renal failure results in the accumulation of various uremic toxins, which are produced by biological synthetic pathway or microbiome in the circulation. Accumulated uremic toxins exert deleterious and cytotoxic effects on organs, and related to a variety of symptoms and organ-dysfunction in renal failure, such as renal damage, cardiovascular damage, mineral and bone disorder. Recently, it revealed that accumulated uremic toxins, indoxyl sulphate, p-cresyl sulphate and phenyl sulphate, in the circulation are imported into whole body organs in renal failure conditions.

The special issue entitled “The Functional Analysis of Uremic Toxins by Metabolomics ” focuses on understanding the roles of uremic toxins on organ-dysfunction in renal failure conditions. Especially, the studies that examined metabolic alterations by uremic toxins using cell lines, animal renal failure models,  and also clinical study assessed by mass spectrometry are welcome. In addition, the studies that visualized the metabolic alteration and accumulated uremic toxins in tissues using imaging mass spectrometry are also welcome.

Dr. Emiko Sato
Dr. Daisuke Saigusa
Guest Editors

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Keywords

  • Uremic toxins
  • Metabolomics
  • Indoxyl sulphate
  • p-cresyl sulphate
  • Phenyl sulphate
  • Uremic sarcopenia
  • Cognitive impairment
  • Mass spectrometry
  • Chronic kidney disease
  • Microbiome

Published Papers (3 papers)

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Research

12 pages, 2466 KiB  
Article
Wide-Targeted Metabolome Analysis Identifies Potential Biomarkers for Prognosis Prediction of Epithelial Ovarian Cancer
by Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Daisuke Saigusa, Bin Li, Kei Kudo, Keita Tsuji, Shogo Shigeta, Hideki Tokunaga, Kazuki Kumada, Keigo Komine, Hidekazu Shirota, Yuichi Aoki, Ikuko N. Motoike, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto, Seizo Koshiba and Nobuo Yaegashi
Toxins 2021, 13(7), 461; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13070461 - 30 Jun 2021
Cited by 15 | Viewed by 5179
Abstract
Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual’s [...] Read more.
Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual’s current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy. Full article
(This article belongs to the Special Issue The Functional Analysis of Uremic Toxins by Metabolomics)
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13 pages, 2177 KiB  
Article
CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients
by Yasutoshi Akiyama, Koichi Kikuchi, Takafumi Toyohara, Eikan Mishima, Chitose Suzuki, Takehiro Suzuki, Masaaki Nakayama, Yoshihisa Tomioka, Tomoyoshi Soga and Takaaki Abe
Toxins 2021, 13(5), 324; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13050324 - 30 Apr 2021
Cited by 2 | Viewed by 2218
Abstract
Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations [...] Read more.
Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients. Full article
(This article belongs to the Special Issue The Functional Analysis of Uremic Toxins by Metabolomics)
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17 pages, 4101 KiB  
Article
Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease
by Satoshi Kumakura, Emiko Sato, Akiyo Sekimoto, Yamato Hashizume, Shu Yamakage, Mariko Miyazaki, Sadayoshi Ito, Hideo Harigae and Nobuyuki Takahashi
Toxins 2021, 13(1), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010050 - 11 Jan 2021
Cited by 20 | Viewed by 4803
Abstract
Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation [...] Read more.
Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention. Full article
(This article belongs to the Special Issue The Functional Analysis of Uremic Toxins by Metabolomics)
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