尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值

doi:10.3877/cma.j.issn.2095-3216.2016.04.005

中华肾病研究电子杂志 ›› 2016, Vol. 05 ›› Issue (04) : 163 -167. doi: 10.3877/cma.j.issn.2095-3216.2016.04.005

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尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值

陈佳¹, 肖菲¹, 付碧琼¹, 林利容¹, 陈客宏¹, 张建国¹, 李开龙¹, 郑卢权¹, 何娅妮¹^,^†(

)

^1. 400042　重庆，第三军医大学大坪医院野战外科研究所肾内科

收稿日期:2016-05-21 出版日期:2016-08-28
通信作者: 何娅妮
基金资助:
国家自然科学基金面上项目(81470962); 国家十二五科技支撑计划项目子课题(2011BAI10B08)

Value of urinary neutrophil gelatinase-associated lipocalin in evaluation of renal tubulointerstitial injury of type 2 diabetic nephropathy

Jia Chen¹, Fei Xiao¹, Biqiong Fu¹, Lirong Lin¹, Kehong Chen¹, Jianguo Zhang¹, Kailong Li¹, Luquan Zheng¹, Yani He¹^,^†()

^1. Department of Nephrology, Institute of Field Surgery, Daping Hospital Affiliated to Third Military Medical University, Chongqing 400042, China

Received:2016-05-21 Published:2016-08-28
Corresponding author: Yani He
About author:
Corresponding author: He Yani, Email: heynmai@yahoo.com

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陈佳, 肖菲, 付碧琼, 林利容, 陈客宏, 张建国, 李开龙, 郑卢权, 何娅妮. 尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值[J]. 中华肾病研究电子杂志, 2016, 05(04): 163-167.

Jia Chen, Fei Xiao, Biqiong Fu, Lirong Lin, Kehong Chen, Jianguo Zhang, Kailong Li, Luquan Zheng, Yani He. Value of urinary neutrophil gelatinase-associated lipocalin in evaluation of renal tubulointerstitial injury of type 2 diabetic nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2016, 05(04): 163-167.

目的

探讨尿中性粒细胞明胶酶相关载脂蛋白(NGAL)对评价2型糖尿病肾病(DN)患者肾小管间质损伤的价值。

方法

研究对象为2012年1月至2015年12月第三军医大学大坪医院2型糖尿病患者167例(2型糖尿病组)；将2型糖尿病组再分为正常白蛋白尿组(n＝56)、微量白蛋白尿组(n＝58)、大量白蛋白尿组(n＝53)，其中51例患者进行了肾活检。50例非糖尿病患者作为正常对照组。采用酶联免疫吸附测定方法检测尿液中NGAL水平，分光光度法测定尿N-乙酰-β-D-葡萄糖苷酶(NAG)。分析尿NGAL水平与肾功能相关指标[尿NAG、尿白蛋白/肌酐比值(ACR)、eGFR]及肾组织损伤病理评分之间的相关性，以及NGAL对DN肾小管间质损伤严重程度的评价效能，采用SPSS软件进行统计学分析，相关性分析采用Pearson或Spearman方法。

结果

糖尿病患者尿NGAL水平较非糖尿病正常对照组明显增加；尿NGAL水平与尿NAG、ACR呈正相关(r＝0.528, 0.578，P<0.001)，与eGFR呈负相关(r＝－0.637，P<0.001)；尿NGAL水平与DN肾小管萎缩与间质纤维化(IFTA)的严重程度呈显著正相关(r＝0.652，P<0.001)；尿NGAL曲线下面积最大(AUC＝0.868)，特异度94.7%，敏感度71.9%。

结论

尿NGAL是评价DN肾小管间质损伤理想的生物标志物之一。

关键词: 中性粒细胞明胶酶相关载脂蛋白, 糖尿病肾病, 肾小管间质损伤, 生物标志物

Objective

To investigate the value of urinary neutrophil gelatinase-associated lipocalin (NGAL) in evaluation of renal tubulointerstitial injury of type 2 diabetic nephropathy (DN).

Methods

167 patients with type 2 diabetes and 50 patients without diabetes were recruited in this study from the Department of Nephrology of Daping Hospital from January of 2012 to December of 2015. The diabetic patients were categorized into normoalbuminuria group (n=56), microalbuminuria group (n=58), and macroalbuminuria group (n=53), among whom 51 patients received renal biopsies. Urinary NGAL levels were measured by ELISA, and urinary NAG levels were measured by the spectrophotometric method. Analysis was made for correlation of urinary NGAL with renal function parameters, and with renal histopathological sores. The value of urinary NGAL in evaluation of renal tubulointerstitial injury of DN was also analyzed.

Results

Urinary NGAL levels were elevated in diabetic patients compared with the non-diabetes control. Urinary NGAL levels were positively associated with both urinary NAG (r=0.528, P<0.001) and ACR (r=0.578, P<0.001), and negatively associated with eGFR (r=-0.637, P<0.001). Urinary NGAL levels were significantly correlated with scores of renal tubular atrophy and interstitial fibrosis (r=0.652, P<0.001) in DN. Urinary NGAL had the largest area under the curve (AUC=0.868), with a specificity of 94.7% and a sensitivity of 71.9%.

Conclusion

Urinary NGAL could serve as one of the most ideal biomarkers for evaluating the tubulointerstitial injury in DN.

Key words: Neutrophil gelatinase-associated lipocalin, Diabetic nephropathy, Renal tubulointerstitial injury, Biomarker

表1 非糖尿病正常对照组与2型糖尿病组临床资料比较(±s，中位数)

项目	非糖尿病正常对照组(n＝50)	2型糖尿病组
项目	非糖尿病正常对照组(n＝50)	正常白蛋白尿组(n＝56)	微量白蛋白尿组(n＝58)	大量白蛋白尿组(n＝53)
年龄(岁)	61.1±5.6	61.5±9.3	63.1±6.6	62.2±7.3
身体质量指数(kg/m²)	23.3±1.3	24.7±3.0^a	24.8±4.0^a	25.4±4.0^a
收缩压(mmHg)	129.6±12.0	135.2±15.9	142.7±24.9^a	147.2±27.9^ab
舒张压(mmHg)	80.5±7.7	74.9±12.6	74.9±12.4	73.5±12.8^a
降压药物[例(%)]	－	29 (51.8)	37 (63.8)^b	38 (71.7)^b
血肌酐(μmol/L)	66.4(56.5，76.2)	65.4(56.4, 76.0)	71.8(61.3，94.3)^ab	143.9 (105.1，201.5)^abc
eGFR[ml/(min·1.73 m²]	100.8(92.7，108.6)	99.4(90.1，103.3)	92.7(67.8，101.5)^ab	43.6(30.3，64.2)^abc
ACR(mg/gCr)	3.6(2.5, 7.6)	10.6(8.1, 14.9)^a	59.1(39.3，134.0)^ab	1931.7(807.9，3019.4)^abc
尿NAG/肌酐(U/gCr)	5.6(2.9, 7.1)	10.7(5.6, 15.2)^a	13.0(8.5，31.2)^ab	30.4(18.5, 40.6)^abc
尿NGAL/肌酐(ng/gCr)	3.3(2.7, 4.4)	10.9(7.2, 13.4)^a	18.3(7.3，59.1)^ab	107.9(17.6, 359.6)^abc

表1 非糖尿病正常对照组与2型糖尿病组临床资料比较(±s，中位数)

项目	非糖尿病正常对照组(n＝50)	2型糖尿病组
项目	非糖尿病正常对照组(n＝50)	正常白蛋白尿组(n＝56)	微量白蛋白尿组(n＝58)	大量白蛋白尿组(n＝53)
年龄(岁)	61.1±5.6	61.5±9.3	63.1±6.6	62.2±7.3
身体质量指数(kg/m²)	23.3±1.3	24.7±3.0^a	24.8±4.0^a	25.4±4.0^a
收缩压(mmHg)	129.6±12.0	135.2±15.9	142.7±24.9^a	147.2±27.9^ab
舒张压(mmHg)	80.5±7.7	74.9±12.6	74.9±12.4	73.5±12.8^a
降压药物[例(%)]	－	29 (51.8)	37 (63.8)^b	38 (71.7)^b
血肌酐(μmol/L)	66.4(56.5，76.2)	65.4(56.4, 76.0)	71.8(61.3，94.3)^ab	143.9 (105.1，201.5)^abc
eGFR[ml/(min·1.73 m²]	100.8(92.7，108.6)	99.4(90.1，103.3)	92.7(67.8，101.5)^ab	43.6(30.3，64.2)^abc
ACR(mg/gCr)	3.6(2.5, 7.6)	10.6(8.1, 14.9)^a	59.1(39.3，134.0)^ab	1931.7(807.9，3019.4)^abc
尿NAG/肌酐(U/gCr)	5.6(2.9, 7.1)	10.7(5.6, 15.2)^a	13.0(8.5，31.2)^ab	30.4(18.5, 40.6)^abc
尿NGAL/肌酐(ng/gCr)	3.3(2.7, 4.4)	10.9(7.2, 13.4)^a	18.3(7.3，59.1)^ab	107.9(17.6, 359.6)^abc

图1 2型糖尿病组中不同尿白蛋白组间尿NGAL水平比较

表2 糖尿病患者尿NGAL与尿NAG、ACR和eGFR的相关性分析

项目	r值	P值
尿NAG	0.528	<0.001
ACR	0.578	<0.001
eGFR	－0.637	<0.001

表2 糖尿病患者尿NGAL与尿NAG、ACR和eGFR的相关性分析

项目	r值	P值
尿NAG	0.528	<0.001
ACR	0.578	<0.001
eGFR	－0.637	<0.001

表3 糖尿病肾病患者尿NGAL与肾组织损伤评分的相关性分析

项目	r值	P值
肾小球硬化	0.480	<0.001
IFTA	0.652	<0.001
肾间质炎症	0.420	0.002
动脉透明变性	0.347	0.013
动脉硬化	0.180	0.206

表3 糖尿病肾病患者尿NGAL与肾组织损伤评分的相关性分析

项目	r值	P值
肾小球硬化	0.480	<0.001
IFTA	0.652	<0.001
肾间质炎症	0.420	0.002
动脉透明变性	0.347	0.013
动脉硬化	0.180	0.206

图2 ROC曲线分析相关生物标志物对DN肾小管间质损伤的评价效能

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