A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome.
A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome.
复制标题
DOI：
10.1177/1177271917695832
复制
发表时间：
2017
影响因子：
3.8
通讯作者：
Devarajan P
中科院分区：
文献类型：
--
作者：
Bennett MR;Pleasant L;Haffner C;Ma Q;Haffey WD;Ying J;Wagner M;Greis KD;Devarajan P
特发性肾病综合征(NS)是儿童最常见的肾小球疾病。对糖皮质激素初始治疗的反应是预后的一个指标，因为耐药患者往往表现出更多的进展性疾病。在这项横断面的初步研究中，我们着手发现一组非侵入性生物标志物，可以区分激素抵抗型肾病综合征(SRNS)和激素敏感型肾病综合征(SSNS)。从这样一个小组收集的信息可以产生更个性化的治疗计划，并防止不太可能有反应的患者暴露于不必要的类固醇。尿液来自辛辛那提儿童医院医学中心诊断为特发性肾病综合征的50名儿童患者。使用相对和绝对定量等压标签(ITRAQ)在一个5×5的小发现队列中发现了13个在SSNS和SRNS中差异表达的蛋白质。在iTRAQ确定的13个标记中，有9个标记被找到了合适的分析方法，并用于25个SRNS×25个SSNS验证队列。检测维生素D结合蛋白(VDBP)、α-1酸性糖蛋白1(AGP1)、α1酸性糖蛋白2(AGP2)、α1-B糖蛋白(A1BG)、胎球蛋白A、前白蛋白、甲状腺激素结合球蛋白和血凝素、α2巨球蛋白，并与尿中性粒细胞明胶酶相关脂蛋白(NGAL)联合检测。单因素分析发现SRNS患者尿VDBP、前白蛋白、NGAL、胎球蛋白-A和AGP2显著升高，受试者工作特征曲线下面积(AUC)在0.65~0.81之间。多变量分析显示，所有10个标志物的AUC为0.92，用于识别SRNS。5个标记物(包括VDBP、NGAL、胎球蛋白-A、前白蛋白和AGP2)的子集与SRNS显著相关，AUC为0.85。
Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). Information gleaned from such a panel could yield more individualized treatment plans and prevent unnecessary steroid exposure in patients unlikely to respond. Urine was collected from 50 pediatric patients diagnosed with idiopathic NS at Cincinnati Children’s Hospital Medical Center. Isobaric tags for relative and absolute quantitation (iTRAQ) was used to discover 13 proteins that were differentially expressed in SSNS vs SRNS in a small 5 × 5 discovery cohort. Suitable assays were found for 9 of the 13 markers identified by iTRAQ and were used in a 25 SRNS × 25 SSNS validation cohort. Vitamin D–binding protein (VDBP), alpha-1 acid glycoprotein 1 (AGP1), alpha-1 acid glycoprotein 2 (AGP2), alpha-1-B glycoprotein (A1BG), fetuin-A, prealbumin, thyroxine-binding globulin and hemopexin, and alpha-2 macroglobulin were measured and combined with urine neutrophil gelatinase–associated lipocalin (NGAL), which had been previously shown to distinguish patients with SRNS. Urinary VDBP, prealbumin, NGAL, fetuin-A, and AGP2 were found to be significantly elevated in SRNS using univariate analysis, with area under the receiver operating characteristic curves (AUCs) ranging from 0.65 to 0.81. Multivariate analysis revealed a panel of all 10 markers that yielded an AUC of 0.92 for identification of SRNS. A subset of 5 markers (including VDBP, NGAL, fetuin-A, prealbumin, and AGP2) showed significant associations with SRNS and yielded an AUC of 0.85.