Urinary Peptide Signatures Distinguish Overactive Bladder and are Associated with Improvement in Incontinence Following Therapy

This study analyzed urinary peptides from 152 participants, including 100 patients with overactive bladder (OAB) and 52 healthy controls. Urine samples were processed for peptidomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Peptides isolated from samples were identified with PEAKS Online software. Participants completed validated symptom questionnaires at baseline and again following clinical therapy or device-based interventions. Classical statistical testing and machine learning methods were applied to compare peptide composition between groups and to explore associations with symptomatic change.

Overall urinary peptidome composition differed significantly between OAB patients and controls (p = 0.001), and OAB samples contained a greater number of unique peptides (p = 0.001). Specific peptide origins that were more abundant in OAB included fragments mapped to fibrillin-1 and to quiescin sulfhydryl oxidase 1. Random forest classifiers trained on peptide data discriminated OAB from controls with an area under the receiver operating characteristic curve (AUC) of 0.76 overall and 0.91 within the premenopausal subset, indicating stronger classification performance in that subgroup.

Baseline peptide composition also differed between participants who experienced improvement in incontinence after therapy and those who did not (p = 0.03 overall). A similar difference was observed within the subgroup undergoing sacral neuromodulation (p = 0.04). The authors interpret the peptide signature as reflecting extracellular matrix remodeling, oxidative stress, and altered cellular metabolism in OAB. They note these profiles may have potential utility as prognostic biomarkers and underscore the heterogeneous nature of OAB pathophysiology; further validation in additional cohorts is warranted.