Urinary Peptide Signatures Distinguish Overactive Bladder and Are Associated With Improvement in Incontinence...

To characterize urinary peptide signatures in patients with and without overactive bladder (OAB), identify peptide differences by OAB phenotype, and determine the association between baseline peptide profiles and improvement in incontinence following therapy.

Peptidomic analysis using LC-MS/MS on urinary samples from 152 participants (100 OAB patients, 52 healthy controls) was performed. Participants completed validated questionnaires at baseline and following treatment. We isolated urinary peptides, analyzed them by mass spectrometry, and identified them using PEAKS Online software. Classical statistical analyses and random forest machine learning classifiers were used to distinguish OAB from controls, and responders vs nonresponders to therapy.

The urinary peptidome differed significantly between patients with OAB and controls in overall peptide composition (P = .001) and number of unique peptides (P = .001). Peptides from fibrillin-1 and quiescin sulfhydryl oxidase 1 were more abundant in OAB. Random forest classifiers had good discrimination between OAB and controls (AUC 0.76 overall; 0.91 in premenopausal subset). Baseline peptide composition differed between those who experienced improvement in incontinence vs those who did not experience improvement following therapy in the overall cohort (P = .03) and sacral neuromodulation group (P = .04).

OAB is associated with a unique urinary peptide signature that reflects extracellular matrix remodeling, oxidative stress, and altered cellular metabolism. Baseline peptide profiles differ between those who symptomatically improved vs did not improve following therapy suggesting potential utility of urinary peptides as prognostic biomarkers. These findings support the heterogeneous nature of OAB pathophysiology and may facilitate development of new diagnostic and personalized therapeutic approaches.