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Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men

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Abstract

Purpose

To investigate the association between nocturia and urinary metabolites in elderly men using metabolomic analysis.

Methods

We recruited 66 men aged 65–80 years. The 3-day frequency volume chart (FCV), International Prostate Symptom Score (IPSS), and quality of life score were used to assess micturition behavior. Participants with the total IPSS > 0 and ≥ 1.5 micturition on an average for three nights were included in the nocturia group. Participants with the total IPSS < 8 and < 1.5 micturition at night were included in the control group. We conducted a comprehensive metabolomic analysis of urine samples. Metabolites were compared between the groups using an unpaired t test. A multivariable logistic regression analysis was used to determine the relationship between nocturia and these metabolites.

Results

The nocturia and control groups consisted of 45 and 21 men, respectively. There were no differences in the background factors between the groups except for receiving anticholinergic drug and having life style-related diseases. The FVC revealed that nocturnal urine volume, 24 h micturition frequency, and nocturnal micturition frequency were significantly higher in the nocturia group than in the control group. The metabolomic analysis revealed 16 metabolites, which were differentially expressed between the groups. The multivariate analysis showed that increased serotonin level and decreased 3-hydroxypropionic acid and 3-indoleacetonitrile levels were associated with nocturia.

Conclusions

These findings suggest that abnormal urinary metabolites including serotonin, 3-hydroxypropionic acid, and 3-indoleacetonitrile are involved in the pathogenesis of nocturia in elderly men.

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Acknowledgements

This study was funded by Astellas Pharma, Inc. and designed by Astellas Pharma, Inc. in collaboration with the authors.

Funding

This study was funded by Astellas Pharma, Inc.

Author information

Authors and Affiliations

  1. Department of Urology Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan

    Satoru Kira, Takahiko Mitsui, Tatsuya Miyamoto, Tatsuya Ihara, Hiroshi Nakagomi, Sachiko Tsuchiya, Norifumi Sawada & Masayuki Takeda

  2. Pharmacology Research Labs, Astellas Pharma Inc, Tsukuba-shi, Japan

    Yuka Hashimoto, Hajime Takamatsu, Masayuki Tanahashi & Masahiro Takeda

Authors
  1. Satoru Kira
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  2. Takahiko Mitsui
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  3. Tatsuya Miyamoto
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  4. Tatsuya Ihara
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  5. Hiroshi Nakagomi
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  6. Yuka Hashimoto
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  10. Sachiko Tsuchiya
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  11. Norifumi Sawada
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Contributions

SK: data collection, data analysis, manuscript writing. TM: data analysis, manuscript editing. TM: data collection, data analysis. TI: data analysis. HN: data collection, data analysis. YH: data analysis. HT: data analysis. MT: data analysis. MT: data analysis, other (supervision). ST: data management. NS: data analysis. MT: data analysis manuscript editing, other (supervision).

Corresponding author

Correspondence to Satoru Kira.

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Conflict of interest

The study was designed by Astellas Pharma, Inc. in collaboration with the authors. Several of the authors are employees of Astellas Pharma, Inc. The other authors have no potential competing interests to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Kira, S., Mitsui, T., Miyamoto, T. et al. Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men. World J Urol 38, 2563–2569 (2020). https://doi.org/10.1007/s00345-019-03042-9

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  • DOI: https://doi.org/10.1007/s00345-019-03042-9

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