Association of Longitudinal Changes in Symptoms and Urinary Biomarkers in Patients with Urological Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.
Association of Longitudinal Changes in Symptoms and Urinary Biomarkers in Patients with Urological Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.
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DOI：
10.1097/ju.0000000000001391
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Moses MA
中科院分区：
文献类型：
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作者：
Roy R;Stephens AJ;Daisy C;Merritt L;Newcomb CW;Yang J;Dagher A;Curatolo A;Sachdev M;McNeish B;Landis R;van Bokhoven A;El-Hayek A;Froehlich J;Pontari MA;Zurakowski D;Lee RS;Moses MA
分析一系列新型非侵入性尿液生物标志物客观监测UCPPS患者纵向临床状态的能力。收集基线、6个月和12个月的尿液样本（n=216），并通过酶联免疫吸附试验（ELISA）定量血管内皮生长因子（VEGF）、VEGF受体1（VEGF-R1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、基质金属蛋白酶（MMP）-2，MMP-9和MMP-9/NGAL复合物。使用功能聚类算法将患者的症状变化分类为改善、稳定或恶化。比例优势模型用于评估症状变化与尿液生物标志物之间的关联。在所有抽样的参与者中，标准化VEGF浓度（pg/ug）的纵向降低与疼痛严重程度的改善相关，MMP-9、NGAL和VEGF-R1浓度（pg/ml）以及NGAL标准化浓度的降低与泌尿系统症状的改善相关。正常VEGF-R1的纵向降低与中度易尿失禁、无膀胱症状和无疼痛充盈患者的疼痛改善相关。较低的基线标准化VEGF-R1浓度仅与盆腔疼痛患者的疼痛改善相关。在所有参与者中，较高的基线MMP-9/NGAL水平与疼痛和泌尿改善相关。此外，MMP-2浓度的纵向增加与男性和疼痛填充患者的疼痛改善相关。我们的研究结果表明，这些尿生物标志物可能是有用的监测UCPPS症状的变化方面的泌尿系统的严重程度和疼痛的严重程度。通过进一步的测试，它们可以代表UCPPS进展和/或解决的客观生物学指标，同时也可以深入了解UCPPS的病理生理学。
To analyze a series of novel non-invasive urinary biomarkers for their ability to objectively monitor the longitudinal clinical status of UCPPS patients. Baseline, 6- and 12-month urine samples were collected (n=216) and used to quantify vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGF-R1), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-2, MMP-9, and MMP-9/NGAL complex by enzyme-linked immunosorbent assays (ELISA). Patients’ symptom changes were classified as improved, stable, or worse using a functional clustering algorithm. Proportional odds models were used to evaluate the association between symptom change and urinary biomarkers. Across all sampled participants, longitudinal decreases in normalized VEGF concentration (pg/ug) were associated with pain severity improvement, and decreases in MMP-9, NGAL, and VEGF-R1 concentration (pg/ml) as well as NGAL normalized concentration were associated with improved urinary symptoms. Longitudinal decreases in normalized VEGF-R1 were associated with pain improvement in patients with moderate widespreadness, no bladder symptoms and no painful filling. Lower baseline normalized VEGF-R1 concentration was associated with pain improvement in patients with pelvic pain only. Higher baseline MMP-9/NGAL levels were associated with pain and urinary improvement across all participants. Moreover, longitudinal increases in MMP-2 concentration was associated with improved pain in men and patients with painful filling. Our results suggest these urinary biomarkers may be useful in monitoring UCPPS symptom changes with respect to both urinary severity and pain severity. With further testing, they may represent objective biologic measures of UCPPS progression and/or resolution while also providing insight into the pathophysiology of UCPPS.