Expansion of Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) (U01)

09/17/2012, 5:00 PM

To: All Faculty in the School of Nursing


Below please find a limited submission opportunity with only one proposal allowed per institution. If you are interested in applying to this program please email me by September 17, 2012.


Expansion of Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) (U01)


Program Description:

Lower urinary tract dysfunction is common in both men and women, and the incidence and prevalence increase with advancing age. Symptoms of lower urinary tract dysfunction (LUTD) encompass all urinary symptoms including storage, voiding, incontinence, and post-micturition symptoms. Symptoms of LUTD are highly prevalent and occur in both genders to a similar extent, with 51% of men and 59% of women exhibiting storage symptoms; 26% of men and 20% of women exhibiting voiding symptoms; and 17% of men and 14% of women exhibiting post-micturition symptoms.

The impact and burden of symptoms of LUTD to individuals and to the nation are enormous. Those patients with symptoms of LUTD suffer considerable morbidity resulting in a significant decrease in quality of life for both the patient and his/her partner. According to the results from the NIDDK supported Urologic Disease in America project, the diseases related to the prostate, only one of the organs that may contribute to lower urinary tract symptoms, cost 2.5 billion dollars to the nation in 2000 exclusive of outpatient treatments. A recent analysis of the National Health and Nutrition Examination Survey showed that when urinary incontinence was defined as "urine leakage during physical activity, before reaching the toilet, and during nonphysical activity", the prevalence is 51% in women and 14% in men aged 20 years old or older. When the aging of the population is taken into account, the financial challenge caused by bothersome LUTD is expected to increase dramatically. Treatments for these symptom-based disorders are only modestly effective at best, have significant side-effects, wane in their effect over time, and are costly.

The specific term of "Lower Urinary Tract Symptoms" (LUTS) more commonly relates to infravesical obstructive and bladder irritative symptoms excluding urinary incontinence. The canonical "LUTS" has been traditionally attached to a specific urologic organ, the prostate. In men over the age of 50 LUTS is usually attributed to urinary obstruction caused by an enlarged prostate (e.g., benign prostatic hyperplasia, or BPH). However; recent research suggests that common pathophysiological changes (e.g. inflammation, fibrosis, and connective tissue, vascular or neurologic factors) in more than one urologic organ may be responsible for a group of symptoms. Moreover, involvement of non-urological adjacent organs (e.g. colon), remote organs (e.g. brain), other diseases or conditions (e.g. diabetes), medication (e.g. diuretics), or lifestyle factors (e.g. drinking habits) may contribute to the development or modify the severity of lower urinary tract symptom complexes. Thus, the underlying causes for symptoms of LUTD appear more complex than previously appreciated and potentially involve both organ/tissue-specific and more systemic contributions. To address this evolving view, new and novel approaches are needed to better define and categorize different lower urinary tract symptom complexes and identify the underlying cause(s) of observed symptoms and their proportional contribution to overlapping symptom profiles seen in numerous urologic conditions.

Although there are many validated measurement tools used in research evaluating LUTD, they are usually burdensome and do not capture all symptoms related to the lower urinary tract. The American Urological Association symptom score (AUA SS), which was initially intended to objectively quantify the symptoms of BPH patients, is widely used in clinical practice. In addition, it is often used as an endpoint in clinical trials to assess symptom-based clinical improvement in benign lower urinary tract disease. However, objective improvement in symptoms of LUTD following an intervention, does not always correlate with patient expectations, satisfaction and goal achievement, which are critically important for successful management of LUTD. Therefore, overreliance on using the current AUA SS to evaluate all types of symptoms of LUTD limits clinical relevance due to weak correlation with patient satisfaction. This also may be scientifically invalid and impede continued scientific progress in assessing study outcomes relative to symptom bother. Thus, better measurement tools that focus on patient reported outcomes (PRO) are essential to measure early, late, transient, and persistent symptoms of LUTD both in men and women.

Despite years of basic and clinical research, many fundamental questions regarding the etiology and natural history of LUTD remain unanswered. Although epidemiologic studies have uncovered many associations with symptoms of LUTD, there is still a lack of understanding of causality. There is an urgent need for a comprehensive assessment of symptoms of LUTD through phenotyping patients using combined, multidisciplinary approaches, including studies of the natural history of symptoms; structure and function of the lower urinary tract, including contributions of other non-urological factors; interplay between different organs and systems; and biological marker discovery efforts. Special emphasis has to be placed on integrating complimentary epidemiological and basic science approaches to provide a systemic characterization of early symptoms of LUTD, the transient changes, causes and predictors of both progression and response to therapy. Advances and emerging technologies now allow development of better phenotyping methods for individuals with symptomatic conditions. This phenotyping approach should address the long-standing questions in the field and enhance our knowledge allowing for development of improved treatment and prevention strategies.

The goals outlined in this funding initiative were developed in part, based on discussions at the 2011 NIDDK Meeting on Measurement of Urinary Symptoms (MOMUS).

Sponsor Deadlines:

Letter of Intent – October 29, 2012
Full Proposal – November 29, 2012