Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Eur J Hum Genet. 2018 Sep;26(9):1354-1360. doi: 10.1038/s41431-018-0182-7. Epub 2018 Jun 11.
Steroid-resistant nephrotic syndrome represents about 10-20% of pediatrics' nephrotic syndrome. The regeneration of glomerular barrier seems pivotal for cessation of proteinuria. Nephronectin (NPNT) plays a major role in nephrogenesis, signal transduction, and epithelial-mesenchymal interactions. This study aims to preliminary assess NPNT as potential noninvasive biomarker of glomerular regeneration and its ability to identify steroid resistance. In this case control study, 80 retrospectively selected patients with nephrotic syndrome were enrolled in addition to 40 healthy controls. Forty patients were steroid sensitive (SSNS) and the other 40 patients were steroid-resistant (SRNS), NPTN concentration was measured using ELISA and NPNT mRNA expression was assayed using real-time PCR. NPTN concentrations were significantly higher in SSNS than both SRNS and controls (The means were 4.64 ± 3.05, 0.69 ± 0.44, and 1.63 ± 0.59, respectively). Moreover, NPTN concentrations were significantly lower in SRNS than controls. NPTN was significantly overexpressed in SSNS compared to both SRNS and controls (the means were 10.82 ± 7.39, 1.19 ± 0.94, and 1.04 ± 0.10, respectively) with no statistically significant difference between SRNS and controls. ROC curves analysis showed that both NPNT expression and NPNT serum level are of promising diagnostic performance (ROC 0.948 and 0.896, respectively). Regression analysis showed that both NPNT expression and NPNT serum level can be independent predictors of steroid resistance. The present study shows for the first time an enhanced expression of NPNT in steroid-sensitive nephrotic syndrome patients suggesting NPNT as a marker of glomerular regeneration. Also, serum NPNT can be a useful noninvasive biomarker of steroid resistance.
激素耐药性肾病综合征约占儿科肾病综合征的 10-20%。肾小球屏障的再生似乎对蛋白尿的停止至关重要。肾钙黏蛋白(NPNT)在肾发生、信号转导和上皮-间充质相互作用中起主要作用。本研究旨在初步评估 NPNT 作为潜在的肾小球再生非侵入性生物标志物及其识别激素耐药性的能力。在这项病例对照研究中,回顾性选择了 80 例肾病综合征患者,另外选择了 40 例健康对照者。40 例患者为激素敏感型肾病综合征(SSNS),另 40 例患者为激素耐药型肾病综合征(SRNS),采用 ELISA 法测定 NPNT 浓度,实时 PCR 法测定 NPNT mRNA 表达。SSNS 组的 NPNT 浓度明显高于 SRNS 组和对照组(均值分别为 4.64±3.05、0.69±0.44 和 1.63±0.59)。此外,SRNS 组的 NPNT 浓度明显低于对照组。与 SRNS 组和对照组相比,SSNS 组的 NPNT 表达明显上调(均值分别为 10.82±7.39、1.19±0.94 和 1.04±0.10),但 SRNS 组与对照组之间无统计学差异。ROC 曲线分析显示,NPNT 表达和 NPNT 血清水平均具有良好的诊断性能(ROC 分别为 0.948 和 0.896)。回归分析显示,NPNT 表达和 NPNT 血清水平均可作为激素耐药的独立预测因子。本研究首次显示 NPNT 在激素敏感型肾病综合征患者中表达增强,提示 NPNT 可作为肾小球再生的标志物。此外,血清 NPNT 可能是激素耐药的有用非侵入性生物标志物。