Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

中文翻译：

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成人原发性足细胞病引发的特发性肾病综合征的蛋白质组学分析：调节机制和诊断意义

特发性肾病综合征（NS）是一组异质性肾小球疾病，包括两种主要表型：微小病变（MCD）和局灶节段性肾小球硬化（FSGS）。 MCD 和 FSGS 是原发性足细胞病的典型类型。我们的目的是探索原发性足细胞病引发的 NS 的分子机制，并通过分析血液蛋白质组谱来评估所选蛋白质组特征的诊断价值。我们总共招募了两组 90 名参与者。第一个队列使用无标记定量 (LFQ) 蛋白质组学进行分析，以发现差异表达的蛋白质并鉴定 NS 中丰富的生物过程，并进一步研究与肾损伤的临床标志物的关系。使用基于平行反应监测的定量蛋白质组学对第二组进行分析，以验证 LFQ 蛋白质组学的数据，并使用接受者操作特征曲线分析评估所选蛋白质的诊断性能。一些生物过程（如免疫反应、细胞粘附和缺氧反应）被发现与 MCD 和 FSGS 期间的肾损伤有关。此外，三种蛋白（CSF1、APOC3 和 LDLR）在检测由原发性足细胞病引发的成人 NS 方面具有超过 90% 的敏感性和特异性。已确定的生物过程可能在 MCD 和 FSGS 发病机制中发挥至关重要的作用。这三种血液蛋白标记物有望用于诊断由原发性足细胞病引发的成人 NS。