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Metabolomics Approach to Male Lower Urinary Tract Symptoms: Identification of Possible Biomarkers and Po-tential Targets for New Treatments

Purpose
We identified metabolites using a metabolomics approach and investigated the association between these metabolites and lower urinary tract symptoms.

Materials and Methods
We used a 24-hour bladder diary and I-PSS (International Prostate Symptom Score) to assess micturition behavior and lower urinary tract symptoms in 58 male patients without apparent neurological disease. Lower urinary tract symptoms were defined as a total I-PSS score of 8 or greater. Patients with a score of 7 or less were placed in the control group. A comprehensive study of plasma metabolites was also performed by capillary electrophoresis time-of-flight mass spectrometry. Metabolites were compared between the lower urinary tract symptoms and control groups using the Mann-Whitney U test. Biomarkers of male lower urinary tract symptoms from the metabolites were analyzed using multivariable logistic regression analysis to determine the OR.

Results
Of the 58 men 32 were in the lower urinary tract symptoms group and the remaining 26 were in the control group. The 24-hour bladder diary showed that nocturnal urine volume, 24-hour micturition frequency, nocturnal micturition frequency and the nocturia index were significantly higher in the lower urinary tract symptoms group. Metabolomics analysis identified 60 metabolites from patient plasma. Multivariate analysis revealed that increased glutamate and decreased arginine, asparagine and inosine monophosphate were significantly associated with lower urinary tract symptoms in males. Decreases in citrulline and glutamine could also be associated with male lower urinary tract symptoms.

Conclusions
Male lower urinary tract symptoms may develop due to abnormal metabolic processes in some pathways. Potential new treatments for lower urinary tract symptoms can be developed by identifying changes in the amino acid profiles.


Takahiko Mitsui, Satoru Kira, Tatsuya Ihara, Norifumi Sawada, Hiroshi Nakagomi, Tatsuya Miyamoto, Hiroshi Shimura, Hiroshi Yokomichi, Masayuki Takeda
Departments of Urology and Health Sciences (HY), Graduate School of Medical Sciences, University of Yama-nashi, Yamanashi, Japan
The Journal of Urology, May 2018, Volume 199, Issue 5, Pages 1312–1318
DOI: https://doi.org/10.1016/j.juro.2017.11.070

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