人附睾蛋白4作为肾脏纤维化分子诊断标志物的临床价值

Clinical value of HE4 as a molecular marker for renal fibrosis

目的探讨慢性肾脏病(CKD)患者血清人附睾蛋白4(HE4)的变化及其对肾脏纤维化的诊断价值。方法选取2020年1月-2022年1月于武汉市中医医院就诊的159例CKD患者,分为CKD 1~5期组,选择同期健康体检者39例为对照组。比较各组血清HE4、肌酐(Crea)、尿素氮(Bun)及尿液β2微球蛋白(β2-M)水平。采用受试者工作特征(ROC)曲线评价HE4辅助诊断CKD的价值,并通过GEO数据库分析HE4与肾脏纤维化的关系。结果CKD 1~5期患者血清HE4水平分别为(84.36±7.53)pmol/L、(148.90±16.46)pmol/L、(259.80±36.93)pmol/L、(438.80±81.92)pmol/L、(1002.34±68.55)pmol/L,均高于对照组[(33.80±1.99)pmol/L,均P<0.05];且随着CKD的进展,患者血清HE4逐渐升高。血清HE4、Crea、Bun及尿液β2-M预测CKD的曲线下面积分别为0.998、0.801、0.748、0.826,HE4对CKD辅助诊断的敏感性和特异性分别为0.983和0.949。GEO数据库分析发现,HE4基因WFDC2与肾脏纤维化密切相关,不同疾病诱导的肾脏纤维化模型中的WFDC2基因表达均明显升高(均P<0.05)。结论血清HE4水平升高与肾脏纤维化相关,对肾脏纤维化导致的慢性肾功能不全具有较高的临床价值。

Objective To investigate the changes of serum human epididymis protein 4(HE4)in patients with chronic kidney disease(CKD)and its diagnostic value for renal fibrosis.Methods A total of 159 patients with CKD who were treated in Wuhan Hospital of Traditional Chinese Medicine from January 2020 to January 2022 were selected and divided into CKD 1-5 stage groups,and 39 healthy subjects were selected as the control group.The levels of serum HE4,creatinine(Crea),blood urea nitrogen(Bun)and urineβ2-microglobulin(β2-M)in each group were compared.The receiver operating characteristic(ROC)curve was used to evaluate the value of HE4 in the auxiliary diagnosis of CKD.The relationship between HE4 and renal fibrosis was analyzed by GEO database.Results Serum HE4 levels in CKD 1-5 stage patients were(84.36±7.53)pmol/L,(148.90±16.46)pmol/L,(259.80±36.93)pmol/L,(438.80±81.92)pmol/L,and(1002.34±68.55)pmol/L,respectively,were all higher than that of control group[(33.80±1.99)pmol/L,all P<0.05].With the progression of CKD,serum HE4 increased gradually.The areas under the curve of serum HE4,Crea,Bun and urineβ2-M for predicting CKD were 0.998,0.801,0.748 and 0.826,respectively(all P<0.05).The sensitivity and specificity of HE4 for the diagnosis of CKD were 0.983 and 0.949,respectively.GEO database analysis showed that HE4 gene WFDC2 was closely related to renal fibrosis,and WFDC2 gene expression was significantly increased in renal fibrosis models induced by different diseases(all P<0.05).Conclusion Elevated serum HE4 level is associated with renal fibrosis and has a high clinical value for chronic renal insufficiency caused by renal fibrosis.