Inflammatory and Tissue Remodeling Urinary Biomarkers before and after Mid Urethral Sling Surgery for Stress Urinary Incontinence

Abstract

Objective Urinary biomarkers were measured from women at baseline and 1 post-surgery for stress urinary incontinence (SUI) and associations with clinicodemographic covariates and outcomes were analyzed. Methods Pre- and post-surgery urine specimens from 150 women were assayed for inflammatory biomarkers (TNF-α, IFN-γ, IL-1β, IL6, IL10, IL12p70, IL17, NGF) and tissue remodeling biomarkers (collagenase activity, MMPs-1, 2, 9, 13, N-telopeptide cross-linked collagen (NTx), EGF, HB-EGF). Paired t-tests compared changes in biomarker over 1 year (significance p<0.05). Linear regression models correlated baseline and changes in biomarker levels with covariates (significance p≤0.001). Logistic regression models, controlling for age, analyzed associations of baseline and changes in biomarker levels with surgical failure (significance p<0.05). Results Over one year, IL12p70 decreased (0.53±1.4 to 0.28±.62 pg/mg Cr, p=0.04) and NGF increased (0.034 ± 0.046 to 0.044 ± 0.060 pg/ml/mOsm, p=0.03). Baseline NTx level/mg Cr was positively associated with age and post-menopausal status (p=0.001), and negatively associated with current estrogen use (p=0.0001). Baseline collagenase activity/mg Cr was positively associated with age (p=0.001). EGF/mOsm, NTx/mOsm and IFN-γ/mOsm were negatively correlated with age, current estrogen use, and UDI-irritative score, respectively (p≤0.001). Subjects with lower baseline NTx/mg Cr were less likely to experience surgical failure (OR 0.49, 95% CI 0.26, 0.93, p=0.03). Changes in biomarker levels were neither associated with any covariates nor surgical failure. Conclusions Women with lower baseline NTx levels were significantly less likely to fail SUI surgery. Studies are needed to validate NTx as a possible independent biomarker for SUI surgery outcomes.

The Association of Urinary Nerve Growth Factor Levels With Bladder Outlet Obstruction in Women

“…A recent study by Chai et al 13 looked at various urinary biomarkers before and after midurethral sling surgery for stress urinary incontinence. The urinary markers after continence surgery trial studied urinary NGF values in 150 women with stress urinary incontinence before and 1 year after midurethral sling surgery.…”

Circulating matrix metalloproteinases and their tissue inhibitors as markers for ethnic variation in pelvic floor tissue integrity

“…Furthermore, there was no significant difference between plasma levels of markers of collagen synthesis such as pro-collagen type 1-N pro-peptide, MMP-9 and vitamin C in patients with POP and/or SUI and controls. In another study, urinary collagenase assay of factors including MMP-1, -2 and -9 was the optimum pre-operative predictor of mid-urethral sling outcome in women with SUI, and revealed negative correlation with urethral closure pressure (20,21). Recent genotypic studies have identified molecular markers of dysfunction of the supportive pelvic floor connective tissue, with genetic polymorphism of MMP-1 and -9 identified in women with POP compared with controls (22,23).…”

Avaliação dos biomarcadores urinários de inflamação e de remodelação tecidual na disfunção vesical em pacientes com hiperplasia prostática benigna

“…O resultado do nosso estudo difere de outra série que demonstrou níveis urinários diminuídos de MMP-1 em pacientes obstruídos, apresentando uma tendência a ser negativamente correlacionado com a obstrução infravesical, apesar do autor não evidenciar significância estatística (Chai et al, 2014). Contudo, alguns autores demonstraram, em analise tecidual, que um modelo de OIV em ovelhas resultou no desenvolvimento de fibrose vesical e acúmulo de colágeno e matriz extracelular (Peters, 1997).…”

“…Esses resultados estão em concordância com os encontrados em séries que avaliaram os níveis desses biomarcadores em pacientes com SBH e HD (Tyagi et al, 2010;Bouchelouche et al, 2004;Bouchelouche et al, 2006;Alkis et al, 2015;Chai et al, 2014 (Tyagi et al, 2010;Alkis et al;2016;Chai et al, 2014 (Tyagi et al, 2010). A presença de EGF aumentado na urina é sugestivo de reparação tecidual e fibrose em pacientes com SBH e OIV (Tyagi et al, 2010;Chai et al, 2014 (Abrams, 2005). Em alguns casos, os aspectos objetivos e subjetivos podem não se correlacionar.…”

“…Foi observado um nível de expressão do EGF urinário diminuído em pacientes idosas que haviam sido submetidas a procedimento cirúrgico de incontinência urinária após um ano de pós-operatório. Os autores observaram um aumento da atividade da colagenase na urina associada à idade, sugerindo a ocorrência de um aumento da remodelação tecidual em pacientes mais idosas (Chai et al, 2014).…”