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J Urol. 2019 Mar 29:101097JU0000000000000257. doi: 10.1097/JU.0000000000000257. [Epub ahead of print]

Biomarkers implicated in lower urinary tract symptoms: systematic review and pathway analyses.

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Division of Urogynecology & Reconstructive Surgery, Department of Obstetrics & Gynecology, Duke University , Durham , NC.
NorthShore , Glenview , IL.
Arbor Research Collaborative for Health , Ann Arbor , MI.
Department of Obstetrics & Gynecology, University of Iowa Carver College of Medicine , Iowa City , IA.
Department of Obstetrics, Gynecology and Reproductive Sciences of the University of Pittsburgh, Division of Urogynecology and Pelvic Reconstructive Surgery Magee-Womens Hospital of UPMC , Pittsburgh , PA.
Departments of Surgery and Anesthesiology, Washington University School of Medicine , St Louis , MO.
University of Michigan , Ann Arbor , MI.
Feinberg School of Medicine, Northwestern University , Chicago , IL.
Department of Urology, Mayo Clinic , Rochester , MN.
National Institute of Diabetes and Digestive and Kidney Diseases , Bethesda , MD.



Lower urinary tract symptoms (LUTS) are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with LUTS.


PUBMED, EMBASE, and Web of Science were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urologic populations without neurologic disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific LUTS or urologic conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways.


Of 6,150 citations identified, 125 met inclusion criteria. Most studies (93.6%) assessed biomarkers at one time point and were cross-sectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for LUTS. When compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder syndrome, and cell migration/cytoskeleton remodeling pathways that were enriched in female stress incontinence.


Major deficiencies in existing biomarker literature include poor reproducibility of laboratory data, unclear classification of LUTS patients, and lack of adjustment for clinical covariates. Despite limitations, we identified multiple putative pathways where panels of biologic markers need further research.


Overactive bladder; biomarkers; nocturia; stress urinary incontinence; urgency urinary incontinence; voiding dysfunction

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