Nephrotic syndrome with idiopathic membranous nephropathy as a major contributor, is characterized by proteinuria, hypoalbuminemia and oedema. Diagnosis is based on renal biopsy and the condition is treated using immunosuppressive drugs; however nephrotic syndrome treatment efficacy varies among patients. Multi-omic urine analyses can discover new markers of nephrotic syndrome that can be used to develop personalized treatments. For proteomics, a protease inhibitor (PI) is sometimes added at sample collection to conserve proteins but its impact on urine metabolic phenotyping needs to be evaluated. Urine from controls (n = 4) and idiopathic membranous nephropathy (iMN) patients (n = 6) were collected with and without PI addition and analysed using ¹H NMR spectroscopy and UPLC-MS. PI-related data features were observed in the ¹H NMR spectra but their removal followed by a median fold change normalisation, eliminated the PI contribution. PI-related metabolites in UPLC-MS data had limited effect on metabolic patterns specific to iMN. When using an appropriate data processing pipeline, PI-containing urine samples are appropriate for ¹H NMR and MS metabolic profiling of patients with nephrotic syndrome.

中文翻译：

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肾脏疾病中的NMR和MS尿代谢表型在蛋白酶抑制剂存在下适用

以特发性膜性肾病为主要病因的肾病综合征的特征是蛋白尿，低白蛋白血症和水肿。诊断基于肾脏活检，并使用免疫抑制药物治疗。然而，肾病综合征的治疗效果因患者而异。多尿酸尿液分析可以发现可用于开发个性化治疗方法的肾病综合征新标志物。对于蛋白质组学，有时会在样品采集时添加蛋白酶抑制剂（PI）以保存蛋白质，但是需要评估其对尿液代谢表型的影响。收集对照组（n = 4）和特发性膜性肾病（iMN）患者（n = 6）的尿液，分别添加和不添加PI，并使用¹1 H NMR光谱和UPLC-MS。在¹ H NMR光谱中观察到了与PI相关的数据特征，但先去除它们，再进行中位数倍数变化归一化，消除了PI的贡献。UPLC-MS数据中与PI有关的代谢物对iMN特有的代谢模式影响有限。当使用适当的数据处理管道时，含PI的尿液样本适合于肾病综合征患者的¹ H NMR和MS代谢谱分析。