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首页> 外文期刊>Journal of Extracellular Vesicles >Specific renal parenchymal-derived urinary extracellular vesicles identify age-associated structural changes in living donor kidneys
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Specific renal parenchymal-derived urinary extracellular vesicles identify age-associated structural changes in living donor kidneys

机译：特定的肾实质来源的尿液细胞外囊泡可鉴定活体供体肾脏中与年龄相关的结构变化

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Non-invasive tests to identify age and early disease-associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age- and sex-stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal-derived EVs in cell-free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule-intercalated cell and monocyte chemoattractant protein-1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule-1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.
机译：需要非侵入性测试来识别年龄和肾脏内与疾病相关的早期病理。特定数量的尿液细胞外囊泡（EVs）可能会用于这种诊断测试。在捐献肾脏之前，从年龄和性别分层的活体肾脏捐献者中获取随机尿样。移植时对供体肾脏进行活检，以鉴定肾单位肥大（较大的肾小球体积，每个肾小球皮层和平均轮廓的肾小管面积）和肾硬化（纤维化百分比，肾小球硬化百分比和动脉硬化）。通过数字流式细胞术对无细胞尿液中肾实质来源的电动汽车进行定量。评估这些EV人群与肾脏活检组织病理学之间的关系。肾脏捐献者的临床特征（n = 138，年龄范围：20-70岁，女性占50％）在正常范围内。总体而言，女性尿液比男性尿液含有更多的电动汽车。随着年龄的增长，外泌体，近肾小球细胞和足细胞标志物阳性电动汽车的数量减少（p <0.05）。肾单位肥大的人的总EV以及肾小球系膜细胞，壁细胞，Henle环的下肢（简单鳞状上皮），收集肾小管插入的细胞和单核细胞趋化蛋白1标记物（p <0.05）的EV较少。在肾硬化患者中，细胞间粘附分子-1，近肾小管细胞，足细胞，壁细胞，近端肾小管上皮细胞，远端肾小管上皮细胞和集合管细胞阳性的EV数量较少（p <0.05）。带有来自肾盂上皮细胞标志物的电动车与肾单位肥大或肾硬化的任何指标均不相关。因此，源自肾小球和肾单位的特定的EVs群体与潜在的肾脏结构变化相关。需要进一步验证其他队列中的这些发现，以确定其临床实用性。

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