PROJECT SUMMARY /ABSTRACT The primary goals of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) are to identifying important subtypes of patients with LUTS, and to improve the measurement of patient experiences of LUTS. The Network's approach to defining patient subtypes was based on a resampling-based consensus clustering approach using self-reported unbiased patient data. The approach to improving the measurement of patient reports of LUTS was to systematically develop a new, high-quality item bank based on qualitative input from patients, community participants, clinicians, and clinical researchers. After a successful initial 5-year funding cycle, LURN is prepared to build on the knowledge gained and take the next steps with the following Specific Aims: • To test and refine the original clustering model with a cohort including a wider range of symptom severity and a wider range of physiological measures. (Cohort-Based Study) A second, more diverse, cohort of patients with LUTS will be recruited to validate the novel symptom- based clusters identified in LURN I. • To determine phenotypic characteristics of women with lower urinary tract symptoms (LUTS) by measuring the functional components of the lower urinary tract. (Organ-Based Study) We have assembled a battery of urodynamic tests to examine the sensory and motor components of both the bladder and the urethra. • To identify protein-based biomarker signatures of proteins contained within plasma of specific subgroups of men and women with LUTS. (Biomarker Study) We will use samples from a representative subset of the LURN I Observational Cohort to identify clusters of patients based on “biomarker signatures” contained within plasma, specifically groups of up- and down- regulated biomarkers. • To validate a comprehensive outcome tool for men and women with LUTS. (Self-Reported Measures Development) Using the Comprehensive Assessment of Self-reported Urinary Symptoms (CASUS) item bank developed in LURN I, we will refine the CASUS into an outcome tool for determining treatment outcomes. • To characterize lower urinary tract and sexual function by presence, type and severity of diabetes mellitus. (Diabetes Study) All LURN II participants will complete a protocol at baseline that includes: surveys querying diabetes experience, autonomic testing, and blood specimen collection for metabolic markers.