Lower urinary tract symptoms (LUTS) affect and afflict a huge portion of the population, with increasing prevalence with advancing age. The negative impact of LUTS is substantial and wide ranging: LUTS can pose a significant burden to affected individuals and caregivers and is associated with an enormous economic burden.^1,2

In 2012, the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) created the Symptoms of Lower Urinary Tract Dysfunction Research Network, known as LURN, to address the gaps in understanding and treating LUTS. LURN is comprised of 6 academic research sites, scientific officers at NIDDK and a data coordinating center at Arbor Research Collaborative for Health. The goals of LURN are to increase understanding of lower urinary tract dysfunction by 1) improving the measurement of patient experiences of LUTS and 2) identifying and explaining the important subtypes of lower urinary tract dysfunction in men and women. Ultimately, the identification of new and distinct subtypes of these symptom conditions will lead to more effective therapeutic options and improved decision making for the affected patients.

To achieve these goals, LURN leverages the resources of a multicenter, multidisciplinary network structure to gather and analyze data on large numbers of affected patients from around the United States. Over the course of 6 years, we enrolled close to 2,000 men and women with LUTS in LURN studies (see figure). The data from over 1,100 participants in the observational cohort study included medical history, physical examination, urological symptom assessments, treatments, sociodemographics and nonurological co-occurring symptom assessments. Other data collected included brain magnetic resonance imaging; quantitative sensory testing; biological samples for genetic, biochemical and microbiological analysis; and physiological data. Many of these data were collected longitudinally.

Figure. LURN I research sites, study enrollment and data collection.

This rich and comprehensive collection of information allows investigators to examine the multitude of domains impacting the development of LUTS and mechanisms of dysfunction, and provides opportunities for multi-domain analyses above and beyond those of each of the individual components. At the time of this writing, there have been 27 manuscripts published, with many more in progress, and over 75,000 biological samples stored at the NIDDK Central Repository (https://repository.niddk.nih.gov/home/) for use by the broader urological research community.

Some of the immediately translatable findings from the first funding cycle of the network (2012–2018) include the following. LURN investigators devoted significant effort to developing self-reported measures for LUTS. The first product was CASUS, an acronym for Comprehensive Assessment of Self-Reported Urinary Symptoms. The almost 100-item instrument captures most of all LUTS and is the most comprehensive self-report LUTS measure to date.³ It was developed for research purposes to identify subgroups of persons with LUTS. Another research tool is the LURN Symptom Index-29, or LURN SI-29, a 29-item instrument to capture symptoms for measurement of clinical outcomes.⁴ The third product is the LURN SI-10, a short, 10-item instrument for routine clinical use for symptom screening and monitoring.⁵ The instrument is appropriate for both men and women, unlike the currently used questionnaires (eg AUA Symptom Index). It captures more urinary symptoms than other instruments, including stress urinary incontinence, urgency urinary incontinence, post-void dribbling, bladder pain/discomfort and symptom bother. These instruments are freely available for public use and download at the LURN website (https://nih-lurn.org/Resources/Questionnaires).

Another study addressed symptom recall, to answer the question: how reliable are patient recollections of their symptoms? A schedule of bladder diaries and symptom reporting was completed by participants over the course of 30 days. The findings indicated that recalled reports generally tracked pretty well with average daily reports of symptoms, for both men and women, supporting the use of both 7- and 30-day recall periods for the LURN instruments.⁶

A separate objective of LURN is to identify clinically relevant subtypes of LUTS patients, because current diagnostic groups and treatments do not seem to address the heterogeneity of these patients. The observational cohort study followed over 1,100 men and women for 12 months, and some of the findings include:

• increasing urinary incontinence severity, rather than the presence or type of urinary incontinence, was associated with increased depression, anxiety and stress⁷
• central and general obesity were key metabolic factors associated with urinary incontinence and overactive bladder⁸
• a large percentage of men seeking care for lower urinary tract symptoms report some incontinence.⁹ This is a particularly germane point, as questionnaires used for men, such as the AUA Symptom Index or International Prostate Symptom Score, do not query for stress and urgency urinary incontinence and post-void dribbling. This finding motivated the inclusion of certain items on the LURN SI-10.

As part of the effort to subtype patients with LUTS, a novel statistical technique that we are using is consensus cluster analysis. Without the bias of these patients’ actual clinical diagnoses, we are using the multi-domain data to see how this heterogeneous group of patients subdivides itself from an unsupervised mathematical standpoint.¹⁰ This work has not yet been clinically validated, but we believe that this new approach to identify subgroups of LUTS patients will result in impactful patient care.

In addition to continuing the work from LURN I on subtyping the broad spectrum of participants with LUTS, the second phase of LURN (LURN II, 2019-2024) focuses research efforts on the symptom of urinary urgency. The International Continence Society defines urgency as the sudden onset of a sensation to void that is difficult to defer, which is the motivation for millions of persons worldwide to seek health care. Approximately 840 men and women with urinary urgency (with or without urgency incontinence) are being recruited and will undergo detailed longitudinal data collection for further subtyping in the areas of symptom patterns, central sensitization, physical activity and sleep, and end organ (bladder and urethra) physiology. We will also continue the work of LURN I, by validating the instruments that have been developed.

The efforts of LURN, to improve the measurement of LUTS and to better understand the subtypes of LUTS and their pathophysiology, will ultimately bring forward better treatments and treatment decision making for these prevalent and burdensome conditions.