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Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses.

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.

SUBMITTER: Siddiqui NY

PROVIDER: S-EPMC6766427 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses.

Siddiqui Nazema Y NY Helfand Brian T BT Andreev Victor P VP Kowalski Joseph T JT Bradley Megan S MS Lai H Henry HH Berger Mitchell B MB Mueller Margaret G MG Bickhaus Jennifer A JA Packiam Vignesh T VT Fenner Dee D Gillispie Brenda W BW Kirkali Ziya Z

The Journal of urology 20191009 5

<h4>Purpose</h4>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.<h4>Materials and methods</h4>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 neurologi ...[more]

PMID: 30925127

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Project description:ContextAlthough family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS.ObjectiveTo systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations.Evidence acquisitionA systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies.Evidence synthesisWe identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49-0.83) with moderate heterogeneity (I(2)=27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes.ConclusionsFew putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses.Patient summaryCombining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations.

Project description:OBJECTIVES:We aimed to synthesise the available data for the effect of stopping alpha-blocker therapy among men with lower urinary tract symptoms. The focus was on symptom, uroflowmetry and quality of life outcomes, but we also reviewed the adverse events (AEs) and the number of patients who restarted therapy. DATA SOURCES:We searched MEDLINE/PubMed, EMBASE/Ovid and The Cochrane Central Register of Controlled Trials from inception to May 2018. ELIGIBILITY CRITERIA:We selected studies regardless of study design in which men were treated with an alpha-blocker for at least 3 months and in which the effects of alpha-blocker discontinuation were subsequently studied. Only controlled trials were used for the primary objective. DATA EXTRACTION AND SYNTHESIS:Two reviewers independently extracted data and assessed the risk of bias for the controlled studies only using the Cochrane Collaboration's tool for assessing risk of bias. Data were pooled using random-effects meta-analyses. RESULTS:We identified 10 studies (1081 participants) assessing the primary objective. Six studies (733 participants) assessed differences in AEs between continuation and discontinuation, and six studies (501 participants) reported the numbers of subjects that restarted treatment after discontinuation. No studies in primary care were identified. After discontinuing monotherapy, symptom scores increased and peak flow rates decreased at 3 and 6 months, but not at 12 months; however, neither parameter changed when alpha-blockers were stopped during combination therapy. Small differences in post-void residual volumes and quality of life scores were considered clinically irrelevant. We also found that 0%-49% of patients restarted after stopping alpha-blocker therapy and that AEs did not increase with discontinuation. CONCLUSIONS:Discontinuing alpha-blocker monotherapy leads to a worsening compared with continuing therapy. Discontinuing the alpha-blocker after combination therapy had no significant effects on outcomes in either the short or long term. Discontinuation may be appropriate for the frail, elderly or those with concomitant illness or polypharmacy. However, studies in primary care are lacking. PROSPERO REGISTRATION NUMBER:CRD42016032648.

Dataset Information

Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses.

Publications

Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses.

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