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首页> 外文期刊>Kidney International Reports >Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Metabolomics
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Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Metabolomics

机译：血浆代谢组学预测和定义小儿肾病综合征的类固醇耐药性

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IntroductionNephrotic syndrome (NS) is a kidney disease that affects both children and adults. Glucocorticoids have been the primary therapy for >60 years but are ineffective in approximately 20% of children and approximately 50% of adult patients. Unfortunately, patients with steroid-resistant NS (SRNS; vs. steroid-sensitive NS [SSNS]) are at high risk for both glucocorticoid-induced side effects and disease progression.MethodsWe performed proton nuclear magnetic resonance (1H NMR) metabolomic analyses on plasma samples (n?= 86) from 45 patients with NS (30 SSNS and 15 SRNS) obtained at initial disease presentation before glucocorticoid initiation and after approximately 7 weeks of glucocorticoid therapy to identify candidate biomarkers able to either predict SRNS before treatment or define critical molecular pathways/targets regulating steroid resistance.ResultsStepwise logistic regression models identified creatinine concentration and glutamine concentration (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.99–1.02) as 2 candidate biomarkers predictive of SRNS, and malonate concentration (OR: 0.94; 95% CI: 0.89–1.00) as a third candidate predictive biomarker using a similar model (only in children >3 years). In addition, paired-sample analyses identified several candidate biomarkers with the potential to identify mechanistic molecular pathways/targets that regulate clinical steroid resistance, including lipoproteins, adipate, pyruvate, creatine, glucose, tyrosine, valine, glutamine, and sn-glycero-3-phosphcholine.ConclusionMetabolomic analyses of serial plasma samples from children with SSNS and SRNS identified elevated creatinine and glutamine concentrations, and reduced malonate concentrations, as auspicious candidate biomarkers to predict SRNS at disease onset in pediatric NS, as well as additional candidate biomarkers with the potential to identify mechanistic molecular pathways that may regulate clinical steroid resistance.
机译：简介肾病综合征（NS）是一种肾脏疾病，会影响儿童和成人。糖皮质激素已成为60多年来的主要治疗方法，但在约20％的儿童和约50％的成人患者中无效。不幸的是，类固醇抵抗性NS患者（SRNS;对类固醇敏感性NS [SSNS]）处于糖皮质激素诱导的副作用和疾病进展的高风险中。方法我们对血浆进行了质子核磁共振（1H NMR）代谢组学分析在糖皮质激素治疗开始前和糖皮质激素治疗约7周后的初始疾病表现中获得的45例NS患者（30例SSNS和15例SRNS）的样本（n = 86），以识别能够预测治疗前SRNS或定义关键分子的候选生物标志物结果逐步逐步逻辑回归模型确定了肌酸酐浓度和谷氨酰胺浓度（几率[OR]：1.01; 95％置信区间[CI]：0.99-1.02）作为2个预测SRNS的候选生物标志物和丙二酸浓度（或：0.94; 95％CI：0.89–1.00）作为使用相似模型的第三个候选预测生物标志物（仅适用于3岁以上的儿童）。此外，配对样本分析还发现了几种候选生物标志物，它们有可能识别调节临床类固醇耐药性的分子机制/靶标，包括脂蛋白，己二酸，丙酮酸，肌酸，葡萄糖，酪氨酸，缬氨酸，谷氨酰胺和sn-glycero-3结论对来自SSNS和SRNS患儿的系列血浆样品进行了代谢组学分析，确定了肌酐和谷氨酰胺浓度升高，丙二酸浓度降低，这是预测SRNS在小儿NS发病时的吉祥候选生物标志物，以及潜在的其他候选生物标志物以确定可能调节临床类固醇耐药性的机械分子途径。

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