Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria however, some patients may have slow decline of renal function despite lower level of urinary protein excretion. The different mechanical (visco-elastic) and chemical properties, as well as the proteome profiles of urinary proteins might explain their tubular toxicity mechanism. Brillouin light scattering (BLS) and surface enhanced Raman scattering (SERS) spectroscopies are non-contact, laser optical-based techniques providing visco-elastic and chemical property information of probed human biofluids. We proposed to study and compare these properties of urinary proteins using BLS and SERS spectroscopies in nephrotic patient and validate hybrid BLS-SERS spectroscopy in diagnostic of urinary proteins as well as their profiling. The project ultimately aims for the development of an optical spectroscopic sensor for rapid, non-contact monitoring of urine samples from patients in clinical settings. BLS and SERS spectroscopies will be used for non-contact assessment of urinary proteins in proteinuric patients and healthy subjects and will be cross-validated by Liquid Chromatography-Mass Spectrometry (LC-MS). Participants will be followed-up during the 1 year and all adverse events such as exacerbation of proteinuria, progression of CKD, complications of nephrotic syndrome, disease relapse rate and inefficacy of treatment regimen will be registered referencing incident dates. Associations between urinary protein profiles (obtained from BLS and SERS as well as LC-MS) and adverse outcomes will be evaluated to identify most unfavored protein profiles. This prospective study is focused on the development of non-contact hybrid BLS - SERS sensing tool and its clinical deployment for diagnosis and prognosis of proteinuria. We will identify the most important types of urine proteins based on their visco-elasticity, amino-acid profile and molecular weight responsible for the most severe cases of proteinuria and progressive renal function decline. We will aim for the developed hybrid BLS - SERS sensor, as a new diagnostic & prognostic tool, to be transferred to other biomedical applications. The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT04311684). The date of registration was March 17, 2020.

中文翻译：

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开发和验证混合布里渊-拉曼光谱，用于非接触评估作为肾脏疾病生物标志物的尿液蛋白质的机械化学特性。

蛋白尿是慢性肾病 (CKD) 进展的主要标志物和心血管死亡率的预测因子。预计蛋白尿水平较高的患者肾功能衰竭会迅速发展，但有些患者尽管尿蛋白排泄水平较低，但肾功能可能会缓慢下降。不同的机械（粘弹性）和化学特性，以及尿蛋白的蛋白质组特征可能解释了它们的肾小管毒性机制。布里渊光散射 (BLS) 和表面增强拉曼散射 (SERS) 光谱是非接触式、基于激光的光学技术，可提供探测的人体生物流体的粘弹性和化学性质信息。我们建议在肾病患者中使用 BLS 和 SERS 光谱研究和比较尿蛋白的这些特性，并验证混合 BLS-SERS 光谱在尿蛋白诊断及其分析中的作用。该项目的最终目标是开发一种光谱传感器，用于在临床环境中对患者的尿液样本进行快速、非接触式监测。BLS 和 SERS 光谱将用于非接触式评估蛋白尿患者和健康受试者的尿蛋白，并将通过液相色谱-质谱 (LC-MS) 进行交叉验证。参与者将在 1 年内随访所有不良事件，如蛋白尿加重、CKD 进展、肾病综合征并发症、疾病复发率和治疗方案无效将参考事件发生日期进行登记。将评估尿蛋白谱（从 BLS 和 SERS 以及 LC-MS 获得）与不良结果之间的关联，以确定最不利的蛋白质谱。这项前瞻性研究的重点是非接触式混合 BLS-SERS 传感工具的开发及其用于蛋白尿诊断和预后的临床部署。我们将根据导致蛋白尿和进行性肾功能下降的最严重病例的粘弹性、氨基酸特征和分子量确定最重要的尿蛋白类型。我们的目标是将开发的混合 BLS - SERS 传感器作为一种新的诊断和预后工具，转移到其他生物医学应用中。该试验已获得 ClinicalTrials.gov 的批准（试验注册 ID NCT04311684）。注册日期为2020年3月17日。