Nazema Y Siddiqui1, Brian T Helfand2, Victor P Andreev3, Joseph T Kowalski4, Megan S Bradley5, H Henry Lai6, Mitchell B Berger7, Margaret G Mueller8, Jennifer A Bickhaus1, Vignesh T Packiam9, Dee Fenner7, Brenda W Gillispie7, Ziya Kirkali10. 1. Division of Urogynecology & Reconstructive Surgery, Department of Obstetrics & Gynecology, Duke University, Durham, North Carolina. 2. NorthShore, Glenview, Illinois. 3. Arbor Research Collaborative for Health, Ann Arbor, Michigan. 4. Department of Obstetrics & Gynecology, University of Iowa Carver College of Medicine, Iowa City, Iowa. 5. 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, Pennsylvania. 6. Departments of Surgery and Anesthesiology, Washington University School of Medicine, St. Louis, Missouri. 7. University of Michigan, Ann Arbor, Michigan. 8. Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 9. Department of Urology, Mayo Clinic, Rochester, Minnesota. 10. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Abstract
PURPOSE: Lower urinary tract symptoms 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 lower urinary tract symptoms. MATERIALS AND METHODS: 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 urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. RESULTS: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 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 lower urinary tract symptoms. 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. CONCLUSIONS: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.
PURPOSE: Lower urinary tract symptoms 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 lower urinary tract symptoms. MATERIALS AND METHODS: 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 urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. RESULTS: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 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 lower urinary tract symptoms. 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. CONCLUSIONS: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.
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