Department of Paediatrics and Nephrology, Medical University of Białystok, Białystok, Poland.
Dis Markers. 2013;34(5):357-62. doi: 10.3233/DMA-130980.
The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. We hypothesized that matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) is a better marker of focal sclerosis in the glomerulus then matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) and matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 MMP2/TIMP-2.
The present study used a sample of 36 children and adolescents subdivided into two groups: I - 20 children with MCNS, subjected to examination twice: A - in relapse of nephrotic syndrome, before treatment and B - after regression of proteinuria; II - 16 children with FSGS. MMPs and TIMPs and NGAL levels were measured in the urine using ELISA kit. MMP-9/TIMP-1, MMP-2/TIMP-2 and MMP-9/NGAL ratios were calculated.
Median NGAL/cr. was significantly higher in MCNS and FSGS patients when compared to healthy controls. Both, NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Contrary to FSGS children, in MCNS group, before treatment only NGAL/cr., but not MMP-9/cr. was increased. Urinary concentrations of NGAL and MMP-9 were highly associated with each other (NGAL/cr. vs. MMP-9/cr., r=0.485, p<0.01). Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We also found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) - 9.0; confidence interval (CI) 1.97-41.07].
MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children.
本研究旨在寻找新的生物标志物，用于区分儿童微小病变肾病综合征（MCNS）和局灶节段性肾小球硬化症（FSGS）。我们假设基质金属蛋白酶-9/中性粒细胞明胶酶相关脂质运载蛋白（MMP-9/NGAL）是肾小球局灶性硬化的一个比基质金属蛋白酶-9/基质金属蛋白酶组织抑制剂-1（MMP-9/TIMP-1）和基质金属蛋白酶-2/基质金属蛋白酶组织抑制剂-2（MMP-2/TIMP-2）更好的标志物。
本研究使用了 36 名儿童和青少年的样本，分为两组：I - 20 名 MCNS 患儿，分为两次检查：A - 在肾病综合征复发时，治疗前和 B - 蛋白尿缓解后；II - 16 名 FSGS 患儿。使用 ELISA 试剂盒检测尿液中的 MMPs 和 TIMPs 及 NGAL 水平。计算 MMP-9/TIMP-1、MMP-2/TIMP-2 和 MMP-9/NGAL 比值。
与健康对照组相比，MCNS 和 FSGS 患者的中位 NGAL/cr.明显升高。与对照组相比，FSGS 患者的 NGAL 和 MMP-9 尿水平均显著升高。与 FSGS 患儿不同，在 MCNS 组中，仅在治疗前，NGAL/cr.而不是 MMP-9/cr.升高。NGAL 和 MMP-9 的尿浓度之间高度相关（NGAL/cr.与 MMP-9/cr.，r=0.485，p<0.01）。FSGS 患者的尿 MMP-9/NGAL 比值中位数明显高于 MCNS 患者。我们还发现，MMP-9/NGAL 的显著增加与 FSGS 相关[比值比（OR）-9.0；95%置信区间（CI）1.97-41.07]。
MMP-9/NGAL 比值可作为儿童肾病中 MCNS 和 FSGS 的鉴别标志物。
