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

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

Abstract

Abstract:

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

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsbyjdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-3216.2016.04.005

https://zhsbyjdzzz.cma-cmc.com.cn/EN/Y2016/V05/I04/163

Figures/Tables 5

References 17

[1]	KDOQI. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease[J]. Am J Kidney Dis, 2007, 49(2 Suppl 2): S12-S154.
[2]	Tang SC,Lai KN. The pathogenic role of the renal proximal tubular cell in diabetic nephropathy[J]. Nephrol Dial Transplant, 2012, 27(8): 3049-3056.
[3]	Okada T,Nagao T,Matsumoto H, et al. Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria[J]. Nephrology, 2012, 17(1): 68-75.
[4]	Nauta FL,Boertien WE,Bakker SJ, et al. Glomerular and tubular damage markers are elevated in patients with diabetes[J]. Diabetes Care, 2011, 34(4): 975-981.
[5]	Waanders F,Navis G,van Goor H, et al. Urinary tubular biomarkers of kidney damage: potential value in clinical practice[J]. Am J Kidney Dis, 2010, 55(5): 813-816.
[6]	Roblesosorio ML,Sabath E. Tubular dysfunction and non-albuminuric renal disease in subjects with type 2 diabetes mellitus[J]. Rev Invest Clin, 2014, 66(3): 234-239.
[7]	Macisaac RJ,Ekinci EI,Jerums G. Markers of and risk factors for the development and progression of diabetic kidney disease[J]. Am J Kidney Dis, 2014, 63(2 Suppl 2): 39-62.
[8]	Hojs R,Ekart R,Bevc S, et al. Biomarkers of renal disease and progression in patients with diabetes[J]. J Clin Med, 2015, 4(5): 1010-1024.
[9]	National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update[J]. Am J Kidney Dis, 2012, 60(5): 850-886.
[10]	Bolignano D,Donato V,Coppolino G, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage[J]. Am J Kidney Dis, 2008, 52(3): 595-605.
[11]	Ding H,He Y,Li K, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy[J]. Clin Immunol, 2007, 123(2): 227-234.
[12]	Tervaert TW,Mooyaart AL,Amann K, et al. Pathologic classification of diabetic nephropathy[J]. J Am Soc Nephrol, 2010, 21(4): 556-563.
[13]	Verzola D,Gandolfo MT,Gaetani G, et al. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2008, 295(5): F1563-F1573.
[14]	Gilbert RE,Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury?[J]. Kidney Int, 1999, 56(5): 1627-1637.
[15]	Thomas MC,Burns WC,Cooper ME. Tubular changes in early diabetic nephropathy[J]. Adv Chronic Kidney Dis, 2005, 12(2): 177-186.
[16]	Kim SS,Song SH,Kim IJ, et al. Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients[J]. Diabetes Res Clin Pract, 2012, 97(2): 251-257.
[17]	Liu F,Yang H,Chen H, et al. High expression of neutrophil gelatinase－associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats[J]. Adv Med Sci, 2015, 60(1): 133-138.

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

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

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

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

Please choose a citation manager

Content to export