The urinary metabonome in lower urinary tract symptoms
File(s)
Author(s)
Bray, Rhiannon
Type
Thesis
Abstract
BACKGROUND: Lower urinary tract symptoms (LUTS), including urinary incontinence,
urgency and nocturia, affect approximately half of women worldwide. Despite their
prevalence, the underlying mechanisms causal of LUTS are poorly understood, which is likely
a reflection of a multifactorial aetiology. Current diagnostic methods for LUTS are invasive
and costly, while available treatments are limited by side effects leading to poor patient
compliance. As a result, much recent research has been directed toward identifying novel,
non-invasive biomarkers that have strong diagnostic and prognostic value. However, the
majority of those identified lack specificity or have minimal prognostic benefit.
Metabonomics is the quantitative assessment of metabolites and small molecule changes
involved in biochemical processes thereby offering a direct assessment of system and local
metabolic status.
AIM: In this study, we aimed to identify urine metabolic signatures associated with LUTS using
proton nuclear magnetic resonance (1H-NMR) spectroscopy and to assess whether profiling
and/ or subsequent multivariate analysis would be useful to characterise metabolic
perturbations associated with individual lower urinary tract symptoms and overactive
bladder.
METHODS: Women attending urogynaecology and gynaecology clinics completed the
validated International Consultation on Incontinence – Female Lower Urinary Tract Symptoms
Questionnaire. Asymptomatic control patients were defined as those with normal scores for
bladder pain and all storage and incontinence symptom items. Participants provided midstream
urine samples and metabolic profiles were acquired using 1H-NMR. Resulting spectral
data were assessed using a combination of unsupervised and supervised multivariatemodelling techniques with discriminatory metabolites identified using 1D- and 2Ddimensional
NMR based approaches.
RESULTS: A total of 214 urine samples were collected from women attending tertiary
urogynaecology clinics (cases; n=176) and healthy control women attending general
gynaecology clinics (n=36). High variation in the urine metabolome was observed across the
cohort however analysis of the data using the KODAMA (knowledge discovery by accuracy
maximization) algorithm identified associations between urine metabolic profiles and BMI,
parity, overactive bladder syndrome, frequency, straining and bladder storage. Partition around menoids clustering of the KODAMA data identified four urinary metabotypes, one of
which was associated with increased urinary frequency and decreased BMI.
CONCLUSION: Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying aetiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
urgency and nocturia, affect approximately half of women worldwide. Despite their
prevalence, the underlying mechanisms causal of LUTS are poorly understood, which is likely
a reflection of a multifactorial aetiology. Current diagnostic methods for LUTS are invasive
and costly, while available treatments are limited by side effects leading to poor patient
compliance. As a result, much recent research has been directed toward identifying novel,
non-invasive biomarkers that have strong diagnostic and prognostic value. However, the
majority of those identified lack specificity or have minimal prognostic benefit.
Metabonomics is the quantitative assessment of metabolites and small molecule changes
involved in biochemical processes thereby offering a direct assessment of system and local
metabolic status.
AIM: In this study, we aimed to identify urine metabolic signatures associated with LUTS using
proton nuclear magnetic resonance (1H-NMR) spectroscopy and to assess whether profiling
and/ or subsequent multivariate analysis would be useful to characterise metabolic
perturbations associated with individual lower urinary tract symptoms and overactive
bladder.
METHODS: Women attending urogynaecology and gynaecology clinics completed the
validated International Consultation on Incontinence – Female Lower Urinary Tract Symptoms
Questionnaire. Asymptomatic control patients were defined as those with normal scores for
bladder pain and all storage and incontinence symptom items. Participants provided midstream
urine samples and metabolic profiles were acquired using 1H-NMR. Resulting spectral
data were assessed using a combination of unsupervised and supervised multivariatemodelling techniques with discriminatory metabolites identified using 1D- and 2Ddimensional
NMR based approaches.
RESULTS: A total of 214 urine samples were collected from women attending tertiary
urogynaecology clinics (cases; n=176) and healthy control women attending general
gynaecology clinics (n=36). High variation in the urine metabolome was observed across the
cohort however analysis of the data using the KODAMA (knowledge discovery by accuracy
maximization) algorithm identified associations between urine metabolic profiles and BMI,
parity, overactive bladder syndrome, frequency, straining and bladder storage. Partition around menoids clustering of the KODAMA data identified four urinary metabotypes, one of
which was associated with increased urinary frequency and decreased BMI.
CONCLUSION: Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying aetiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
Version
Open Access
Date Issued
2019-10
Date Awarded
2020-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Bennett, Phillip Robert
Khullar, Vikram
MacIntyre, David Alan
Publisher Department
Department of Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)