World Journal of Urology

, Volume 37, Issue 10, pp 2199–2205 | Cite as

Liquid chromatography–mass spectrometry identification of serum biomarkers for nocturia in aged men

  • Satoru KiraEmail author
  • Takahiko Mitsui
  • Tatsuya Miyamoto
  • Tatsuya Ihara
  • Hiroshi Nakagomi
  • Yuka Hashimoto
  • Hajime Takamatsu
  • Masayuki Tanahashi
  • Masahiro Takeda
  • Norifumi Sawada
  • Karl-Erik Andersson
  • Masayuki Takeda
Original Article



We aimed to investigate the association between nocturia and serum metabolites identified using metabolomics analysis.


This study enrolled 66 men aged 65–80 years, recruited from the outpatient department of a university hospital. The participants were stratified as follows: Nocturia group [45 men with any total international prostate symptom score (IPSS) and an average of 3 nights ≥ 1.5 micturitions/night] and Control group (21 men with total IPSS < 8 and an average of 3 nights < 1.5 micturitions/night). The 24-h frequency–volume chart, IPSS, and Quality-of-Life questionnaire were used to evaluate micturition behavior. Serum metabolite profiles were obtained using liquid chromatography–mass spectrometry (LC–MS)-based metabolomics analysis and compared between the two groups using the unpaired t test. The relationship between serum metabolites and nocturia was determined using multivariable logistic regression analysis.


There were no differences in background factors between the Nocturia and Control groups. In the IPSS, mean total scores in the Nocturia and Control groups were 12.4 and 4.0, respectively. On frequency–volume chart analysis, nocturnal urine volume and micturition frequency during daytime and nighttime were significantly higher in the Nocturia group. LC–MS highlighted 13 serum metabolites as potential biomarkers of nocturia. On multivariate analysis, increased levels of palmitoylethanolamide, 4-hydroxydocosahexaenoic acid, 9-hydroxyoctadecadienoic acid, 20-hydroxydocosahexaenoic acid, 13-hydroxyoctadecadienoic acid, arachidonoylethanolamide, eicosapentaenoic acid, 12-hydroxy-eicosatetraenoic acid, and arachidonic acid were associated with nocturia.


In aged men, the pathogenesis of nocturia involves abnormal metabolism in several signaling pathways involving omega-3 and omega-6 polyunsaturated fatty acids, as well as endocannabinoids.


Nocturia Aged Liquid chromatography mass spectrometry Metabolomics 



This study was funded by Astellas Pharma, Inc. and designed by Astellas Pharma, Inc. in collaboration with the authors. We thank Ms. Sachiko Tsuchiya for her assistance with data management.

Author contribution

SK: data collection, data analysis, and manuscript writing. TM: data analysis and manuscript editing. TM: data collection and data analysis. TI: data analysis. HN: data collection and data analysis. YH: data analysis. HT: data analysis. MT: data analysis. MT: data analysis and other (supervision). NS: data analysis. K-EA: manuscript editing and other (supervision). MT: data analysis, manuscript editing, and other (supervision)


This study was funded by Astellas Pharma, Inc.

Compliance with ethical standards

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.

Informed consent

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


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Satoru Kira
    • 1
    Email author
  • Takahiko Mitsui
    • 1
  • Tatsuya Miyamoto
    • 1
  • Tatsuya Ihara
    • 1
  • Hiroshi Nakagomi
    • 1
  • Yuka Hashimoto
    • 2
  • Hajime Takamatsu
    • 2
  • Masayuki Tanahashi
    • 2
  • Masahiro Takeda
    • 2
  • Norifumi Sawada
    • 1
  • Karl-Erik Andersson
    • 3
  • Masayuki Takeda
    • 1
  1. 1.Department of Urology, Interdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiYamanashiJapan
  2. 2.Pharmacology Research LabsAstellas Pharma IncTsukubaJapan
  3. 3.Institute for Regenerative MedicineWake Forest University School of MedicineWinston-SalemUSA

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