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Urinary metabolomics predict the severity of overactive bladder syndrome in an aging female population

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Abstract

Introduction and hypothesis

To identify urinary metabolites that can facilitate the diagnosis and the characterization of the underlying pathophysiology of the association between the overactive bladder syndrome (OAB) and metabolic syndrome.

Methods

We used gas chromatography-mass spectrometry to compare the urinary metabolome of 20 females of 50–80 years of age with OAB to that of 20 controls of the same age group. We performed urinary metabolomic analysis and obtained serum markers of metabolic syndrome for each subject. Participants completed a clinical evaluation and validated self-reported questionnaires of lower urinary tract symptoms as well as a one-day voiding diary.

Results

In the OAB subjects, we identified increased urinary levels of markers of mitochondrial dysfunction (itaconate, malate and fumarate), oxidative stress (L-pyroglutamate and α-hydroxyglutarate) and ketosis (α-hydroxybutyrate and α-hydroxyisobutyrate). The increased levels of these markers correlated significantly with the OAB symptoms score on questionnaires. We found, using a multiple linear regression model, that age, blood glucose and urine metabolites (malate, fumarate and α-hydroxyisobutyrate) were significant predictive factors of OAB severity. Fumarate had high sensitivity as a biomarker of OAB due to metabolic syndrome, based on a statistically significant receiver-operating characteristic (ROC) curve, indicating its potential as a diagnostic tool.

Conclusions

Altogether, these findings establish that urinary metabolites of mitochondrial dysfunction, ketosis and oxidative stress can be potential biomarkers of OAB severity and diagnosis.

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Abbreviations

OAB:

Overactive bladder syndrome

MetS:

Metabolic syndrome

ROC:

Receiver-operating characteristic

HOMA-IR:

Homeostatic Model Assessment of Insulin Resistance

GFR:

Glomerular filtration rate

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Acknowledgements

Metabolite measurements were performed at the Rosalind and Morris Goodman Cancer Research Centre Metabolomics Core Facility supported by the Terry Fox Foundation oncometabolism team grant (#1048) in partnership with Fondation du cancer du Sein du Quebec (FCSQ), The Dr. John R. and Clara M. Fraser Memorial Trust and McGill University.

Funding

Funding was provided by the Urology Care Foundation Rising Star in Urology Research Award and the Quebec Network for Research on Aging.

Author information

Author notes

  1. Abubakr H. Mossa and Samer Shamout contributed equally to this work.

Authors and Affiliations

  1. Lady Davis Institute for Medical Research, McGill University, 3755, Chemin de la Côte-Ste-Catherine, Montreal, QC, H3T 1E2, Canada

    Abubakr H. Mossa, Samer Shamout, Philippe Cammisotto & Lysanne Campeau

  2. Division of Urology, Department of Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    Samer Shamout & Lysanne Campeau

Authors
  1. Abubakr H. Mossa
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  2. Samer Shamout
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  3. Philippe Cammisotto
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  4. Lysanne Campeau
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Contributions

AM: data collection and manuscript writing.

SS: data collection and manuscript writing.

PC: data collection and manuscript writing.

LC: project development and manuscript writing.

Corresponding author

Correspondence to Lysanne Campeau.

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Mossa, A.H., Shamout, S., Cammisotto, P. et al. Urinary metabolomics predict the severity of overactive bladder syndrome in an aging female population. Int Urogynecol J 31, 1023–1031 (2020). https://doi.org/10.1007/s00192-019-04175-6

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  • DOI: https://doi.org/10.1007/s00192-019-04175-6

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