血清人附睾蛋白4对慢性肾脏疾病的临床诊断价值

李秀义; 齐向明; 夏圆圆; 罗锐; 韩树葳; 余小琴

doi:10.16766/j.cnki.issn.1674-4152.002455

血清人附睾蛋白4对慢性肾脏疾病的临床诊断价值

doi: 10.16766/j.cnki.issn.1674-4152.002455

1.
合肥市第一人民医院安徽医科大学第三附属医院检验科，安徽合肥 230061
2.
安徽医科大学第二附属医院肾内科，安徽合肥 230601

基金项目:

安徽省自然科学基金项目 1908085MH245

详细信息

通讯作者:
余小琴，E-mail：xiaoqin6828@126.com

中图分类号: R692
计量
- 文章访问数: 245
- HTML全文浏览量: 285
- PDF下载量: 10
- 被引次数: 0
出版历程
- 收稿日期: 2021-11-11
- 网络出版日期: 2022-09-05

Clinical value of serum human epididymal protein 4 in the diagnosis of chronic kidney disease

1.
Department of Clinical Laboratory, the First People's Hospital of Hefei (the Third Affiliated Hospital of Anhui Medical University), Hefei, Anhui 230061, China

摘要

摘要: 目的探讨血清人附睾蛋白4(HE4)对慢性肾脏疾病(CKD)及不同分期的临床诊断价值。方法选取2019年2月—2020年9月合肥市第一人民医院肾病科收治的117例CKD患者作为观察组，同期年龄相当的健康体检者78例设为对照组。检测2组受试者血清HE4、尿素氮(BUN)、肌酐(SCr)、胱抑素C(CysC)和视黄醇结合蛋白(RBP)表达水平，比较其2组之间差异，观察其相关性及对CKD临床诊断价值。结果 CKD组患者血清HE4、BUN、SCr、CysC和RBP表达水平明显高于对照组(均P＜0.01)。随着患者CKD分期的上升，CKD各期与对照组比较，BUN和SCr和RBP的早期分组与对照组相比较差异无统计学意义(均P＞0.05), 其余各分期组与对照组相比较差异均有统计学意义(均P＜0.01)；CKD 1~5各分期组间比较发现，HE4、CysC和RBP各组间相比较差异均有统计学意义(均P＜0.05)，BUN和SCr各组间相比较，CKD 1与CKD 2之间差异无统计学意义(均P＞0.05)，CKD 3~CKD 5组间以及与CKD 1~CKD 2比较，差异均有统计学意义(均P＜0.01)。血清HE4的表达水平与eGFR呈负相关关系；与BUN、SCr、CysC及RBP呈正相关关系。ROC分析显示HE4的曲线下面积为(AUC=0.978)明显优于Bun(AUC=0.956)、SCr(AUC=0.973)、CysC(AUC=0.992)和RBP(AUC=0.910)。结论血清HE4水平变化与CKD的发生发展有关，对CKD的分期有一定的临床意义，有望为CKD进展及预后预测提供新的血清生物学诊断标记物。
- 慢性肾脏疾病 /
- 人附睾蛋白4 /
- 肾功能 /
- 诊断价值
Abstract: Objective To investigate the clinical diagnostic value of serum human epididymal protein 4 (HE4) in chronic kidney disease (CKD) and different stages. Methods A total of 117 patients with CKD admitted to the Department of Nephrology of Hefei First People's Hospital from February 2019 to September 2020 were selected as the observation group, and 78 healthy patients with the same age during the same period were selected as the control group. The expression levels of serum HE4, urea nitrogen (BUN), creatinine (SCr), cystatin C (CysC) and retinol-binding protein (RBP) in the subjects of the two groups were detected to observe the correlation and clinical diagnostic value of CKD. Results The expression levels of serum HE4, BUN, SCr, CysC and RBP in the CKD group were significantly higher than those in the control group (all P < 0.01). As the CKD stage of the patients increased, no significant difference in the early grouping of BUN, SCr and RBP was found compared with the control group in each stage of CKD and the control group (all P>0.05). The other staging groups were compared with the control group, and the differences were statistically significant (all P < 0.01). The comparison amongst the CKD 1 - 5 staging groups revealed that the HE4, CysC and RBP groups had statistically significant differences (all P < 0.05), and BUN and SCr were significantly different (all P < 0.05). Compared between groups, there was no significant difference between CKD 1 and CKD 2 (all P>0.05), and significant differences were noted between the CKD 3 and CKD 5 groups and compared with CKD 1 to CKD 2 (all P < 0.01). The expression level of serum HE4 was negatively correlated with eGFR but positively correlated with BUN, SCr, CysC and RBP. ROC analysis showed that the area under the curve of HE4 (AUC=0.978) was significantly better than that of Bun (AUC=0.956), SCr (AUC=0.973), CysC (AUC=0.992) and RBP (AUC=0.910). Conclusion The serum HE4 level is related to the occurrence and development of CKD, and it has certain clinical significance for the staging of CKD. Serum HE4 is expected to function as a new serum biological diagnostic marker for the progression and prognosis of CKD.
- Chronic kidney disease /
- Human epididymal protein 4 /
- Renal function /
- Diagnostic value

HTML全文

图 1 血清HE4、BUN、SCr、CysC和RBP表达水平对CKD的ROC曲线

Figure 1. ROC curve of serum HE4, BUN, SCr, CysC and RBP expression levels on CKD

下载: 全尺寸图片幻灯片

表 1 2组血清HE4、BUN、SCr、CysC和RBP表达水平比较(x±s)

Table 1. The expression levels of HE4, BUN, SCr, CysC and RBP in serum were compared between the two groups(x±s)

组别	例数	HE4(pmol/L)	BUN(pmol/L)	SCr(μmol/L)	CysC(mg/L)	RBP(mg/L)
对照组	78	58.93±8.69	4.73±0.69	55.03±5.49	0.71±0.09	57.83±12.36
CKD组	117	906.82±545.12	15.78±8.01	380.96±233.37	3.45±1.45	110.98±42.93
t值		16.821	14.840	15.101	20.381	12.630
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

下载: 导出CSV

表 2 CKD不同分期组与对照组血清HE4、BUN、SCr、CysC和RBP表达水平比较(x±s)

Table 2. The expression levels of serum HE4, BUN, SCr, CysC and RBP were compared between different stages of CKD and the control group(x±s)

组别	例数	HE4(pmol/L)	BUN(pmol/L)	SCr(μmol/L)	CysC(mg/L)	RBP(mg/L)
对照组	78	58.93±8.69	4.73±0.69	55.03±5.49	0.71±0.09	57.83±12.36
CKD 1组	15	85.75±22.81	4.90±0.65^a	55.12±6.98^a	0.88±0.14	62.92±8.04^a
CKD 2组	20	260.00±128.00	5.05±0.62^ab	58.6±10.95^ab	1.28±0.10	70.27±4.54
CKD 3组	23	254.58±66.38	9.16±2.28	130.52±14.74	1.91±0.21	81.50±9.50
CKD 4组	30	457.22±177.51	14.18±3.69	199.92±37.91	2.83±0.35	97.14±13.97
CKD 5组	29	1 189.56±453.97	20.68±6.75	459.78±155.00	5.19±1.72	123.72±12.14
F值		4.528	9.127	8.274	13.998	12.761
P值		< 0.001	0.017	0.021	< 0.001	< 0.001
注：对照组比较，^aP＞0.05；与CKD 1组比较，^bP＞0.05；其余同项目下组间两两比较差异均有统计学意义(均P＜0.05)。

下载: 导出CSV

参考文献(24)

[1]	LIU Y, LI M Y, SONG Y X, et al. Association of serum bilirubin with renal outcomes in Han Chinese patients with chronic kidney disease[J]. Clinica Chimica Acta, 2018, 480: 9-16. doi: 10.1016/j.cca.2018.01.041
[2]	TARR M C, HINGORANI S R. Prematurity and future kidney health: The growing risk of chronic kidney disease[J]. Curr Opin Pediatr, 2018, 30(2): 1-8.
[3]	李财昌, 周萍, 王顺, 等. 重症医学科患者急性肾损伤的临床特点分析[J]. 新疆医科大学学报, 2017, 40(5): 602-605. doi: 10.3969/j.issn.1009-5551.2017.05.011 LI C C, ZHOU P, WANG S, et al. Clinical characteristics of patients with acute renal injury in intensive care unit[J]. Journal of Xinjiang Medical University, 2017, 40(5): 602-605. doi: 10.3969/j.issn.1009-5551.2017.05.011
[4]	HALTIA U M, HALLAMAA M, TAPPER J, et al. Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Mullerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors[J]. Gynecol Oncol, 2017, 144(1): 83-89. doi: 10.1016/j.ygyno.2016.11.018
[5]	SCALETTA G, PLOTTI F, LUVERO D, et al. The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: A systematic review[J]. Expert Rev Anticancer Ther, 2017, 17(9): 827-839. doi: 10.1080/14737140.2017.1360138
[6]	JIA M M, DENG J, CHENG X L, et al. Diagnostic accuracy of urine HE4 in patients with ovarian cancer: A meta-analysis[J]. Oncotarget, 2017, 8(6): 9660-9671. doi: 10.18632/oncotarget.14173
[7]	张剑, 董欣敏, 吴婧, 等. 血清人附睾蛋白4在肺癌诊断中的临床应用探讨[J]. 中华全科医学, 2016, 14(8): 1302-1304. doi: 10.16766/j.cnki.issn.1674-4152.2016.08.018 ZHANG J, DONG X M, WANG J, et al. The diagnostic value of human epididymis protein 4 in lung cancer[J]. Chinese general practice, 2016, 14(8): 1302-1304. doi: 10.16766/j.cnki.issn.1674-4152.2016.08.018
[8]	潘凌峰, 王静, 陈永伟, 等. 血清人附睾上皮分泌蛋白4水平检测在卵巢癌的应用价值研究[J]. 国际检验医学杂志, 2019, 40(A01): 182-184. https://www.cnki.com.cn/Article/CJFDTOTAL-SFCZ201504013.htm PAN L F, WANG J, CHEN Y W, et al. Study on the application value of serum human epididymal epithelial secretory protein 4 level in ovarian cancer[J]. International Journal of Laboratory Medicine, 2019, 40(A01): 182-184. https://www.cnki.com.cn/Article/CJFDTOTAL-SFCZ201504013.htm
[9]	BÉLA N J, BÉLA N, LIBOR F, et al. Human Epididymis Protein 4: A novel serum inflammatory biomarker in cystic fibrosis[J]. Chest, 2016, 150(3): 661-672. doi: 10.1016/j.chest.2016.04.006
[10]	WANG J L, ZHAO H Y, XU F F, et al. Human epididymis protein 4 (HE4) protects against cystic pulmonary fibrosis associated-inflammation through inhibition of NF-κB and MAPK singnaling[J]. Genes & Genomics, 2019, 41(9): 1045-1053.
[11]	WAN J X, WANG Y H, CAI G R, et al. Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease[J]. Oncotarget, 2016, 7(42): 67748-67759. doi: 10.18632/oncotarget.11682
[12]	WANG L S, SUN Y H, CAI X A, et al. The diagnostic value of human epididymis protein 4 as a novel biomarker in patients with renal dysfunction[J]. Int Urol Nephrol, 2018, 50(2): 2043-2048.
[13]	YANG Z X, ZHANG Z Y, QIN B D, et al. Human epididymis protein 4: A novel biomarker for lupus nephritis and chronic kidney disease in systemic lupus erythematosus[J]. J Clin Lab Anal, 2016, 30(6): 897-904. doi: 10.1002/jcla.21954
[14]	QIN L, MOHAN C. Non-invasive biomarkers for systemic lupus erythematosus: A lookback at 2016[J]. Int J Rheum Dis, 2016, 19(12): 1209-1215. doi: 10.1111/1756-185X.13075
[15]	INKER L A, ASTOR B C, FOX C H, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD[J]. Am J Kidney Dis, 2014, 63(5): 713-735. doi: 10.1053/j.ajkd.2014.01.416
[16]	SIMONA F, CRISTINA R, NICOLETTA T, et al. Serum human epididymis protein 4 vs. carbohydrate antigen 125 in ovarian cancer follow-up[J]. Clin Biochem, 2018, 60: 84-90. doi: 10.1016/j.clinbiochem.2018.08.003
[17]	STIEKEMA A, LOK C, KORSE C M, et al. Serum HE4 is correlated to prognostic factors and survival in patients with endometrial cancer[J]. Virchows Archiv, 2017, 470(6): 655-664. doi: 10.1007/s00428-017-2115-1
[18]	GUNDUZ U R, GUNALDI M, ISIKSACAN N, et al. A new marker for breast cancer diagnosis human epididymis protein 4: A preliminary study[J]. Mol Clin Oncol, 2016, 5(2): 355-360. doi: 10.3892/mco.2016.919
[19]	GE X, ZHANG X L, LI M, et al. The value of serum HE4 in pancreatic adenocarcinoma diagnosis[J]. Int Clinical Exp Pathol, 2017, 10(5): 5618-5623.
[20]	ZENG Q, LIU M Q, ZHOU N, et al. Serum human epididymis protein 4(HE4) may be a better tumor marker in early lung cancer[J]. Clinica Chimica Acta, 2016, 455(1): 102-106.
[21]	LEBLEU V S, TENG Y Q, O' CONNELL J T, et al. Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis[J]. Nat Med, 2013, 19(2): 227-231. doi: 10.1038/nm.2989
[22]	白冰, 张冬萍, 王萍, 等. 肾移植术后CKD患者血清HE4与疾病进展分期的关系及诊断价值[J]. 国际检验医学杂志, 2019, 40(22): 2767-2770. doi: 10.3969/j.issn.1673-4130.2019.22.019 BAI B, ZHANG D P, WANG P, et al. The relationship between serum HE4 and disease progression stage in patients with CKD after renal transplantation and its diagnostic value[J]. International Journal of Laboratory Medicine, 2019, 40(22): 2767-2770. doi: 10.3969/j.issn.1673-4130.2019.22.019
[23]	卢美红, 杨春兰, 景蓉蓉, 等. 血清人附睾蛋白4表达与慢性肾脏病的相关性研究[J]. 现代检验医学杂志, 2017(32): 75-77, 81. https://www.cnki.com.cn/Article/CJFDTOTAL-SXYN201702020.htm LU M H, YANG C L, JING R R, et al. Study on association with expression in patients with chronic kidney disease[J]. Journal of Modern Laboratory Medicine, 2017(32): 75-77, 81. https://www.cnki.com.cn/Article/CJFDTOTAL-SXYN201702020.htm
[24]	QU W L, LI J P, DUAN P, et al. Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies[J]. Exp Rev Mol Diagn, 2016, 16(12): 1271-1282. doi: 10.1080/14737159.2016.1251317