Temporal Changes in Blood Metabolome Among Patients on Hemodialysis

Introduction: Hemodialysis (HD) sustains millions of lives but is associated with poor clinical outcomes. Metabolite accumulation undoubtedly accounts for some of the excess morbidity and mortality in this population; specific toxins responsible for this are not well-defined. Methods: This prospecti...

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Main Authors: Vida Dehghan Niestanak, Natasha Wiebe, Lun Zhang, David S. Wishart, Marcello Tonelli, Larry D. Unsworth
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925001974
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author Vida Dehghan Niestanak
Natasha Wiebe
Lun Zhang
David S. Wishart
Marcello Tonelli
Larry D. Unsworth
author_facet Vida Dehghan Niestanak
Natasha Wiebe
Lun Zhang
David S. Wishart
Marcello Tonelli
Larry D. Unsworth
author_sort Vida Dehghan Niestanak
collection DOAJ
description Introduction: Hemodialysis (HD) sustains millions of lives but is associated with poor clinical outcomes. Metabolite accumulation undoubtedly accounts for some of the excess morbidity and mortality in this population; specific toxins responsible for this are not well-defined. Methods: This prospective study investigates temporal metabolite changes in adults after HD initiation for 60 months or until death or end of study; patients on home or nocturnal HD, peritoneal dialysis, or with a functioning kidney transplant were censored for follow-up. Overall, 267 participants were selected; however, only 241 of these had required samples for analysis at the baseline, 137 at 6 months, 116 at 12 months, and 43 at 60 months. Samples were taken before HD sessions, 80 metabolites isolated from the serum using methanol were quantified using mass spectroscopy techniques, and their concentrations were regressed onto time and participant, using mixed regression in their natural and natural logarithm units. Results: Despite maintenance HD treatment, 74 quantified metabolites showed that 43 significantly increased and 4 significantly decreased in serum concentration over the study period. Of the 43 metabolites that increased in serum concentration over the study period, 24 have not been associated with kidney failure previously. In post hoc analyses, we found that lower water solubility appeared more likely to exhibit increases of metabolites concentration in blood (P = 0.04). Conclusion: The metabolome of patients with kidney failure on maintenance HD changes significantly over 60 months. Future work on correlating toxins and clinical outcomes is needed to drive the development of technologies that improve blood purification for people with kidney failure.
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spelling doaj-art-52647f10366749108c5d95ffae3ca98c2025-08-20T02:06:06ZengElsevierKidney International Reports2468-02492025-06-011061761177010.1016/j.ekir.2025.03.054Temporal Changes in Blood Metabolome Among Patients on HemodialysisVida Dehghan Niestanak0Natasha Wiebe1Lun Zhang2David S. Wishart3Marcello Tonelli4Larry D. Unsworth5Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, CanadaDepartment of Medicine, University of Alberta, Edmonton, Alberta, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada; Correspondence: Larry D. Unsworth, DICE 13-390, University of Alberta, Edmonton, Alberta T6G 2V4, Canada.Introduction: Hemodialysis (HD) sustains millions of lives but is associated with poor clinical outcomes. Metabolite accumulation undoubtedly accounts for some of the excess morbidity and mortality in this population; specific toxins responsible for this are not well-defined. Methods: This prospective study investigates temporal metabolite changes in adults after HD initiation for 60 months or until death or end of study; patients on home or nocturnal HD, peritoneal dialysis, or with a functioning kidney transplant were censored for follow-up. Overall, 267 participants were selected; however, only 241 of these had required samples for analysis at the baseline, 137 at 6 months, 116 at 12 months, and 43 at 60 months. Samples were taken before HD sessions, 80 metabolites isolated from the serum using methanol were quantified using mass spectroscopy techniques, and their concentrations were regressed onto time and participant, using mixed regression in their natural and natural logarithm units. Results: Despite maintenance HD treatment, 74 quantified metabolites showed that 43 significantly increased and 4 significantly decreased in serum concentration over the study period. Of the 43 metabolites that increased in serum concentration over the study period, 24 have not been associated with kidney failure previously. In post hoc analyses, we found that lower water solubility appeared more likely to exhibit increases of metabolites concentration in blood (P = 0.04). Conclusion: The metabolome of patients with kidney failure on maintenance HD changes significantly over 60 months. Future work on correlating toxins and clinical outcomes is needed to drive the development of technologies that improve blood purification for people with kidney failure.http://www.sciencedirect.com/science/article/pii/S2468024925001974kidney failurehemodialysismetabolitesuremic toxins
spellingShingle Vida Dehghan Niestanak
Natasha Wiebe
Lun Zhang
David S. Wishart
Marcello Tonelli
Larry D. Unsworth
Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
Kidney International Reports
kidney failure
hemodialysis
metabolites
uremic toxins
title Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
title_full Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
title_fullStr Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
title_full_unstemmed Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
title_short Temporal Changes in Blood Metabolome Among Patients on Hemodialysis
title_sort temporal changes in blood metabolome among patients on hemodialysis
topic kidney failure
hemodialysis
metabolites
uremic toxins
url http://www.sciencedirect.com/science/article/pii/S2468024925001974
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