Elevated Levels of Urinary Podocyte-Derived Microparticles in Nephrotic Syndrome

Eka Laksmi Hidayati, Bambang Supriyatno, Sudung Oloan Pardede, Partini Pudjiastuti Trihono, Dewi Sukmawati, Dewi Wulandari, Oke Rina Ramayani
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Abstract

BACKGROUND: Nephrotic syndrome (NS) is the most common glomerular disease in childhood. The proposed hypothesis for the pathogenesis of this disease has changed over time, from immune dysregulation theory and systemic circulating factors theory, to the growing recognition of podocytopathies’ role. The existance of podocytopathies is usually examined by using podocyte-derived microparticles (MPs), such as nephrin, podocin, and podocalyxin (PCX). Therefore in this study, the difference between nephrin, podocin, and PCX expressions in NS children and healthy children was investigated.METHODS: An observational cross-sectional study was conducted, involving 33 children with NS and 22 age-matched healthy children as controls. Urine samples were collected from each subject in the early morning, before being processed and incubated with antibodies to detect nephrin, podocin, and PCX. The processed samples were then analyzed with flow cytometer methods.RESULTS: NS subjects had significantly higher expression of all three urinary podocyte-derived MPs compared to the control subjetcs. Nephrin, podocin, and PCX showed good discrimination in NS subjects with the area under curve (AUC) of 0.895, 0.849, and 0.728, respectively.CONCLUSION: This study revealed the differential expression of podocyte proteins in NS subjects compared to healthy controls. This supports the role of podocytopathies in the pathogenesis of NS. Therefore, nephrin, podocin, and PCX might have potentials to be future non-invasive diagnostic tools in glomerular disease.KEYWORDS: nephrin, nephrotic syndrome, podocalyxin, podocin, podocyte, urinary microparticle
肾病综合征患者尿足细胞衍生微粒水平升高
背景:肾病综合征(NS)是儿童最常见的肾小球疾病。随着时间的推移,关于该病发病机制的假设发生了变化,从免疫失调理论和系统循环因子理论,到对足细胞病变作用的日益认识。足细胞病变的存在通常通过足细胞衍生微粒(MPs)来检查,如nephrin、podocin和podocalyxin (PCX)。因此,本研究探讨了NS儿童与健康儿童中nephrin、podocin和PCX表达的差异。方法:进行了一项观察性横断面研究,包括33名NS儿童和22名年龄匹配的健康儿童作为对照。每个受试者在清晨收集尿液样本,然后处理并与抗体孵育以检测nephrin, podocin和PCX。处理后的样品用流式细胞仪进行分析。结果:与对照组相比,NS受试者的所有三种尿足细胞来源MPs的表达均显著增加。Nephrin、podocin和PCX在NS受试者中具有较好的识别能力,曲线下面积(AUC)分别为0.895、0.849和0.728。结论:本研究揭示了NS受试者足细胞蛋白与健康对照组的差异表达。这支持足细胞病变在NS发病机制中的作用。因此,nephrin, podocin和PCX可能有潜力成为未来肾小球疾病的非侵入性诊断工具。关键词:肾素,肾病综合征,足霉素,足霉素,足细胞,尿微粒
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