中性粒细胞明胶酶相关脂质转运蛋白在儿童原发性肾病综合征尿液中的表达及意义

Expression of urinary neutrophil gelatinase-associated lipocalin and its clinical significance in children with idiopathic nephrotic syndrome

摘要:

目的：研究中性粒细胞明胶酶相关脂质转运蛋白（NGAL）在原发性肾病综合征患儿尿中的水平及其意义。方法：原发性肾病综合征初治患儿34例，经口服泼尼松足量治疗4周尿蛋白未转阴患者归入糖皮质激素耐药型肾病综合征（SRNS）组，尿蛋白转阴患者归入糖皮质激素敏感型肾病综合征（SSNS）组。所有病例在口服泼尼松治疗前、治疗1周、2周、3周、4周时分别收集晨起中段尿，采取ELISA法检测尿液NGAL浓度，同时测得尿中肌酐(Cr)值，采用尿Cr排出量来校正单次尿NGAL水平，比较两组间尿NGAL与Cr比值的表达差异。结果：与SRNS组比较，SSNS组病例尿标本中NGAL/Cr比值在泼尼松治疗3、4周时明显下降（P＜0.05）；与SRNS组比较，SSNS组病例尿标本中β2-MG/Cr比值在泼尼松治疗4周时才开始明显下降。SSNS与SRNS两组病例尿NGAL/Cr与尿蛋白/Cr比值呈正相关(r=0.510，P＜0.01)。ROC曲线下分析结果显示，用药3周后尿NGAL/Cr诊断截点为0.043时，敏感度和特异度分别为100%和79.2%。结论 ：SRNS患儿尿液中NGAL/Cr比值持续维持于高水平，而SSNS患儿尿液中NGAL/Cr比值在泼尼松治疗后逐渐下降，且其下降时间早于β2MG/Cr比值，提示动态监测尿液中NGAL/Cr比值，有助于早期判断原发性肾病综合征的泼尼松治疗效应。

Abstract:

OBJECTIVE: To investigate the urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration in children with idiopathic nephrotic syndrome (INS) and its clinical significance. METHODS: Thirty-four children newly diagnosed with INS received oral prednisone for 4 weeks. Patients whose urinary protein did not become negative were classified as steroid-resistant nephrotic syndrome (SRNS) group, while those whose urinary protein did become negative were classified as steroid-sensitive nephrotic syndrome (SSNS) group. Morning midstream urine specimens were collected from all patients before use of prednisone and after 1, 2, 3, and 4 weeks of treatment with prednisone. Enzyme-linked immunosorbent assay was used to measure the urinary NGAL concentration. Meanwhile, urinary creatinine (Cr) concentration was measured, and urinary NGAL concentration in a single urine collection was adjusted according to the urinary Cr excretion. The two groups were compared in terms of urinary NGAL/Cr ratio. RESULTS: Compared with the SRNS group, the SSNS group had significantly decreased urinary NGAL/Cr ratios after 3 and 4 weeks of prednisone treatment (P<0.05). Compared with the SRNS group, the SSNS group had a significantly decreased urinary β2-MG/Cr ratio after 4 weeks of prednisone treatment (P<0.05). In both groups, urinary NGAL/Cr ratio was positively correlated with urinary protein/Cr ratio (r=0.510, P<0.01). The results of ROC curve analysis showed when diagnostic cut-off point of urinary NGAL/Cr was 0.043 by 3 weeks after treatment, sensitivity and specificity achieved 100% and 79.2% respectively. CONCLUSIONS: Urinary NGAL/Cr ratio remains high in children with SRNS, while this ratio decreases gradually during prednisone treatment in children with SSNS, and it falls ahead of urinary β2-MG/Cr ratio. These results suggest that dynamic monitoring of urinary NGAL/Cr ratio is useful for early judgment of response to prednisone in patients with INS.