Department of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
Department of Urology, University of Massachusetts, Worcester, MA, United States of America.
PLoS One. 2022 Jul 14;17(7):e0270018. doi: 10.1371/journal.pone.0270018. eCollection 2022.
Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-invasive way to enhance surgical decision making for patients and urologists.
We sought to develop a predictive model to identify UPJO patients at risk for reduced renal function.
Prospective cohort study.
Pre-operative urine samples were collected in a prospectively enrolled UPJO biomarker registry at our institution. Urinary MMP-2, MMP-7, TIMP-2, and NGAL were measured as well as clinical characteristics including hydronephrosis grade, differential renal function, t1/2, and UPJO etiology.
Children who underwent pyeloplasty for UPJO.
Primary outcome was reduced renal function defined as MAG3 function <40%. Multivariable logistic regression was applied to identify the independent predictive biomarkers in the original Training cohort. Model validation and generalizability were evaluated in a new UPJO Testing cohort.
We included 71 patients with UPJO in the original training cohort and 39 in the validation cohort. Median age was 3.3 years (70% male). By univariate analysis, reduced renal function was associated with higher MMP-2 (p = 0.064), MMP-7 (p = 0.047), NGAL (p = 0.001), and lower TIMP-2 (p = 0.033). Combining MMP-7 with TIMP-2, the multivariable logistic regression model predicted reduced renal function with good performance (AUC = 0.830; 95% CI: 0.722-0.938). The independent testing dataset validated the results with good predictive performance (AUC = 0.738).
Combination of urinary MMP-7 and TIMP-2 can identify reduced renal function in UPJO patients. With the high sensitivity cutoffs, patients can be categorized into high risk (aggressive management) versus lower risk (observation).
已发现细胞外基质蛋白和参与降解的酶与组织纤维化和肾盂输尿管交界处梗阻（UPJO）有关。在这项研究中，我们开发了一种有前途的尿生物标志物模型，可以识别 UPJO 患者的肾功能降低。这可能成为增强患者和泌尿科医生手术决策的一种非侵入性方法。
我们旨在开发一种预测模型，以识别 UPJO 患者中肾功能降低的风险。
前瞻性队列研究。
在我们机构的前瞻性 UPJO 生物标志物登记处收集术前尿样。测量尿 MMP-2、MMP-7、TIMP-2 和 NGAL 以及临床特征，包括肾积水程度、肾功能差异、t1/2 和 UPJO 病因。
接受肾盂成形术治疗 UPJO 的儿童。
主要结果是定义为 MAG3 功能<40%的肾功能降低。多变量逻辑回归用于确定原始训练队列中的独立预测生物标志物。在新的 UPJO 测试队列中评估模型验证和通用性。
我们纳入了 71 名 UPJO 患者的原始训练队列和 39 名验证队列。中位年龄为 3.3 岁（70%为男性）。通过单变量分析，肾功能降低与 MMP-2 较高（p = 0.064）、MMP-7（p = 0.047）、NGAL（p = 0.001）和 TIMP-2 较低（p = 0.033）相关。将 MMP-7 与 TIMP-2 相结合，多变量逻辑回归模型具有良好的预测性能（AUC = 0.830；95%CI：0.722-0.938）。独立测试数据集验证了结果具有良好的预测性能（AUC = 0.738）。
尿 MMP-7 和 TIMP-2 的组合可以识别 UPJO 患者的肾功能降低。使用高灵敏度截止值，患者可以分为高风险（积极管理）与低风险（观察）。
