目的 探讨IgA肾病患者尿中无创性标志物白细胞介素-6(IL-6)、IL-18、转化生长因子-β1(TGF-β1)、肾损伤分子-1(Kim-1)水平与临床、病理指标的关系以及在临床病情评估中的应用价值.方法 观察解放军总医院肾脏病科2007 年12 月至2008 年4 月首次肾活检明确诊断为IgA肾病的115 例患者,将其作为IgA肾病组,以30 例健康志愿者作为健康对照组、30 例非IgA肾病患者作为疾病对照组(包括轻微病变8 例,微小病变11 例,膜性肾病11 例).应用酶联免疫吸附法(ELISA)测定各组患者尿中IL-6、IL-18、TGF-β1、Kim-1 4 种无创性标志物水平,同时测定相关的临床指标,并对IgA肾病病理损害程度进行半定量评分,分析4 种尿无创性标志物水平与各临床指标、病理指标的相关性.应用SPSS 13.0 版统计软件作统计分析,计数资料采用χ2 检验,计量资料比较采用方差分析,相关分析用直线相关、Spearman 等级相关分析.结果 疾病对照组和IgA肾病组在高血压伴发比例、血尿素氮、血肌酐、血清白蛋白水平上,与健康对照组比较,差异均有统计学意义(P 〈 0.05).按照病理Lee 氏分级(Ⅰ~Ⅴ级),将IgA肾病组分为3 个亚组,轻度组(Ⅰ~Ⅱ级)15 例,中度组(Ⅲ级)63 组,重度组(Ⅳ ~ Ⅴ级)37 例.IgA肾病组尿IL-6、尿IL-18、尿TGF-β1、尿Kim-1水平均较健康对照组明显增高(P 〈 0.05);IgA肾病患者随着病理损害程度的逐渐加重,尿IL-6、尿IL-18、尿TGF-β1、尿Kim-1 水平也随之增高,重度组与轻度组、中度组比较,差异均有统计学意义(P 〈 0.05);IgA肾病患者尿IL-6、尿IL-18、尿TGF-β1、尿Kim-1 水平与肾小球滤过率、肾小球球性硬化程度、肾间质炎细胞浸润、肾间质纤维化、肾小管萎缩程度积分等指标均有不同程度相关;尿TGF-1 与尿Kim-1、尿TGF-1 与尿IL-6 联合诊断IgA肾病病理分级程度,其敏感度分别达82.6%和78.3%,特异度分
Objective To investigate the levels of noninvasive urinary biomarkers interleukin-6 (IL- 6), interleukin-18 (IL-18), transforming growth factor-β1 (TGF-β1), kidney injury molecule - 1 (Kim-1) in the IgA nephropathy patients, and to demonstrate the correlation between noninvasive urinary biomarkers and clinical and histological damages in IgA nephropathy, and to evaluate the clinical application value of these urinary biomarkers. Methods One hundred and fifteen patients were prospectivly observed in the nephropathy department of Chinese People's Liberation Army General Hospital from 2007 December to 2008 April, who were diagnosed as IgA nephropathy firstly through renal biopsy. All the patients with IgA nephropathy were included into IgA nephropathy group and classified according to Lee's histological classification. Thirty patients with non-IgA nephropathy (minor glomerular abnormalities 8 cases, minimal change disease 11 cases, membranous nephropathy 11 cases) entered the disease control group, and 30 healthy adults entered the healthy control group. IL-6, IL-18, TGF-β1 and Kim-1 were detected with enzyme-linked immuno sorbent assay (ELISA). The SPSS 13.0 statistical software was used for statistical analysis. Count data were analyzed with X2 test, and measurement data were compared using the analysis of variance, while the correlation were analyzed with the linear correlation and Spearman rank correlation method. Results Compared with the healthy control group, the disease control group and the IgA nephropathy group had significant differences in hypertensive proportion, serum urea nitrogen level, serum creatinine level, and serum albumin level (P 〈 0.05). According to the Lee's pathological grading, the patients of the IgA nephropathy group were divided into mild group (15 cases), moderate group (63 cases), and severe group (37 cases). The levels of urinary IL-6, IL-18, TGF-β1 and Kim-1 in IgA nephropathy group were higher than those of the healthy control gr