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Metabolic profiling of human plasma and urine in chronic kidney disease by hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry: a pilot study

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Abstract

A typical characteristic of chronic kidney disease (CKD) is the progressive loss in renal function over a period of months or years with the concomitant accumulation of uremic retention solutes in the body. Known biomarkers for the kidney deterioration, such as serum creatinine or urinary albumin, do not allow effective early detection of CKD, which is essential towards disease management. In this work, a hydrophilic interaction liquid chromatography time-of-flight mass spectrometric (HILIC-TOF MS) platform was optimized allowing the search for novel uremic retention solutes and/or biomarkers of CKD. The HILIC-ESI-MS approach was used for the comparison of urine and plasma samples from CKD patients at stage 3 (n = 20), at stage 5 not yet receiving dialysis (n = 20) and from healthy controls (n = 20). Quality control samples were used to control and ensure the validity of the metabolomics approach. Subsequently the data were treated with the XCMS software for multivariate statistical analysis. In this way, differentiation could be achieved between the measured metabolite profile of the CKD patients versus the healthy controls. The approach allowed the elucidation of a number of metabolites that showed a significant up- and downregulation throughout the different stages of CKD. These compounds are cinnamoylglycine, glycoursodeoxycholic acid, 2-hydroxyethane sulfonate, and pregnenolone sulfate of which the identity was unambiguously confirmed via the use of authentic standards. The latter three are newly identified uremic retention solutes.

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Acknowledgements

Jente Boelaert gratefully acknowledges the financial support of the Agency for Innovation by Science and Technology in Flanders (IWT). The Metabolomics Innovation Centre (TMIC, Canada) is acknowledged for providing metabolite standards.

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Authors and Affiliations

  1. Separation Science Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000, Ghent, Belgium

    Jente Boelaert & Frédéric Lynen

  2. Renal Division, Department of Internal Medicine, University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium

    Griet Glorieux, Eva Schepers, Nathalie Neirynck & Raymond Vanholder

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  1. Jente Boelaert
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  2. Frédéric Lynen
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Correspondence to Frédéric Lynen.

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The study protocol was approved by the Ethics Committee of Gent University Hospital, and informed consent was obtained prior to collection of the samples.

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Boelaert, J., Lynen, F., Glorieux, G. et al. Metabolic profiling of human plasma and urine in chronic kidney disease by hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry: a pilot study. Anal Bioanal Chem 409, 2201–2211 (2017). https://doi.org/10.1007/s00216-016-0165-x

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