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

  • Satoru Kira 1,
  • Takahiko Mitsui 1,
  • Tatsuya Miyamoto 1,
  • Tatsuya Ihara 1,
  • Hiroshi Nakagomi 1,
  • Yuka Hashimoto 2,
  • Hajime Takamatsu 2,
  • Masayuki Tanahashi 2,
  • Masahiro Takeda 2,
  • Sachiko Tsuchiya 1,
  • Norifumi Sawada 1,
  • Masayuki Takeda 1
1 Department of Urology Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan 2 Pharmacology Research Labs, Astellas Pharma Inc, Tsukuba-shi, Japan

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.

Prof. Van Kerrebroeck

These Japanese authors investigated the association between nocturia and urinary metabolites in elderly men. In total 66 men (aged 65-80 years) were recruited and assessed with a 3-day frequency volume chart (FCV), the International Prostate Symptom Score (IPSS), and a quality of life score. Men with a total IPSS > 0 and ≥ 1.5 micturition on an average for 3 nights were included in the nocturia group (n=45), and those with a total IPSS < 8 and < 1.5 micturition at night were included in the control group (n=21). A comprehensive metabolomic analysis of urine samples was done and metabolites were compared between the groups. A multivariable logistic regression analysis was used to determine the relationship between nocturia and these metabolites. The FVC showed 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. Their findings suggest that abnormal urinary metabolites are involved in the pathogenesis of nocturia in elderly men.