Verdugo-Molinares Maritza G, Ku-Centurion Marco, Cortes-Sanabria Laura, Lugo-Melchor Yadira O, Pinault Emilie, Evangelista Luis, Ramos-Garcia Cesar O, Marquet Pierre, Melo Zesergio
Biotecnología médica y farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara 44270, Mexico; Unidad de Servicios Analíticos y Metrológicos, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara 44270, Mexico.
Biotecnología médica y farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara 44270, Mexico.
J Proteomics. 2025 Aug 18;321:105523. doi: 10.1016/j.jprot.2025.105523.
Chronic kidney disease is a multifactorial entity characterized by decreased glomerular filtration rate (GFR). The last stage of the disease requires renal replacement therapy or kidney transplantation. As a disease with no treatment at earlier stages, and few biomarkers available, proteomics represent an excellent tool searching for new more efficient biomarkers. Urinary extracellular vesicles are an important source of information for kidney alterations, and their collection is not invasive. In this exploratory study, we worked on urine samples collected from patients at Centro Medico Nacional de Occidente in Guadalajara, Jalisco, and isolated urinary extracellular vesicles (uEVs) by ultracentrifugation. Our objective was to compare the Proteomic Profile of uEVs between Mexican patients with normal kidney function, end-stage renal disease, or kidney transplantation. High resolution mass spectrometry analysis reveals alterations in end-stage renal disease regarding the energy metabolism, cytoskeleton organization and cell motility. Proteomic alterations in transplant patients point towards the conservation of fibrotic process. Important proteins such as cystatins can be proposed as candidates for kidney transplant monitoring, while Gelsolin, a protein with an important role in assessing podocyte damage, stands out as a probable marker of chronic kidney disease. Data are available via ProteomeXchange with identifier PXD065380. SIGNIFICANCE: Chronic Kidney disease is a growing public health burden, increasing each year, and favored by major chronic diseases such as diabetes and hypertension. Although Mexico is one of the countries with the highest incidence of chronic kidney disease, proteomics studies involving Mexican patients had not yet been conducted. uEVs are features of particular interest to study the disease and discover biomarkers. We characterized the uEVs proteomic profile in Mexican patients, providing new insights into the pathogenesis of chronic kidney disease and kidney transplantation disorders. We identified promising biomarker candidates for transplant monitoring, and one as an early indicator of ESRD progression. uEVs may serve as a non-invasive platform for renal disease investigation, potentially offering non-invasive biomarkers for patient monitoring as well as mechanistic insights for future research into kidney pathophysiology.
慢性肾脏病是一种以肾小球滤过率（GFR）降低为特征的多因素疾病。该疾病的最后阶段需要肾脏替代治疗或肾移植。作为一种早期阶段无治疗方法且可用生物标志物较少的疾病，蛋白质组学是寻找更有效新生物标志物的极佳工具。尿细胞外囊泡是肾脏改变的重要信息来源，且其采集是非侵入性的。在这项探索性研究中，我们对从哈利斯科州瓜达拉哈拉市国立西部医疗中心的患者收集的尿液样本进行了研究，并通过超速离心法分离出尿细胞外囊泡（uEVs）。我们的目的是比较墨西哥肾功能正常、终末期肾病或肾移植患者的uEVs蛋白质组图谱。高分辨率质谱分析揭示了终末期肾病在能量代谢、细胞骨架组织和细胞运动方面的改变。移植患者的蛋白质组学改变表明纤维化过程持续存在。诸如胱抑素等重要蛋白质可被提议作为肾移植监测的候选标志物，而凝溶胶蛋白在评估足细胞损伤中起重要作用，是慢性肾脏病的一个可能标志物。数据可通过ProteomeXchange获取，标识符为PXD065380。意义：慢性肾脏病是一个日益加重的公共卫生负担，且逐年增加，糖尿病和高血压等主要慢性疾病使其情况更严重。尽管墨西哥是慢性肾脏病发病率最高的国家之一，但尚未开展涉及墨西哥患者的蛋白质组学研究。uEVs是研究该疾病和发现生物标志物的特别感兴趣的特征。我们对墨西哥患者的uEVs蛋白质组图谱进行了表征，为慢性肾脏病和肾移植疾病的发病机制提供了新见解。我们确定了用于移植监测的有前景的生物标志物候选物，以及一个作为终末期肾病进展的早期指标。uEVs可作为肾脏疾病研究的非侵入性平台，有可能为患者监测提供非侵入性生物标志物，并为未来肾脏病理生理学研究提供机制性见解。
