Richter Holly E, Moalli Pamela, Amundsen Cindy L, Malykhina Anna P, Wallace Dennis, Rogers Rebecca, Myers Deborah, Paraiso Maria, Albo Michael, Shi Haolin, Nolen Tracy, Meikle Susie, Word R Ann
University of Alabama at Birmingham, Birmingham, Alabama.
University of Pittsburgh, Pittsburgh, Pennsylvania.
J Urol. 2017 Jun;197(6):1487-1495. doi: 10.1016/j.juro.2017.01.037. Epub 2017 Jan 13.
We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes.
First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ≤0.01 and p ≤0.004 represented moderate evidence of an association with outcomes.
Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother.
Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.
我们测量了难治性急迫性尿失禁女性患者及对照组在基线时以及接受骶神经调节或膀胱逼尿肌内注射A型肉毒毒素治疗6个月后的尿液生物标志物水平。我们还评估了基线生物标志物与治疗后急迫性尿失禁发作次数及膀胱过度活动症症状困扰结局之间的关联。
从同意参与试验的参与者以及年龄匹配的无急迫性尿失禁女性中收集首次晨尿样本。使用标准化酶联免疫吸附测定法和适当的活性测定法测量反映全身炎症、神经炎症、传入神经递质和组织重塑的生物标志物。通过膀胱过度活动症问卷评估症状困扰程度，并通过膀胱日记确定急迫性尿失禁发作次数。使用线性模型检查基线与6个月时平均生物标志物水平的差异以及急迫性尿失禁发作次数和症状困扰的变化。p≤0.01表示潜在关联的适度证据，p≤0.004表示与结局关联的中度证据。
除原弹性蛋白（p = 0.001）和I型胶原N末端肽（p <0.001）外，病例组和对照组的基线生物标志物水平差异不大。干预6个月后生物标志物水平的变化包括两个治疗组的胶原酶水平均下降（p <0.001），以及A型肉毒毒素治疗组的白细胞介素-8（p = 0.002）和基质金属蛋白酶-9（p <0.001）水平升高。两种治疗方法中较高的基线降钙素基因相关肽水平（p = 0.007）以及A型肉毒毒素治疗组中较高的神经生长因子水平（p = 0.007）与膀胱过度活动症症状困扰减轻程度较小有关。
难治性急迫性尿失禁是一种复杂的病症。这些数据表明，基质重塑和神经肽介导可能参与其病理生理机制及对治疗的反应。
