Evaluation of NGAL, KIM-1, and TIMP-2 as early biomarkers in sepsis-associated acute kidney injury: a prospective clinical cohort study

doi:10.3877/cma.j.issn.2096-1537.2019.02.008

Abstract

Abstract:

Objective

To evaluate the diagnostic value of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in early sepsis-associated acute kidney injury (AKI).

Methods

From June 2015 to January 2016, patients with sepsis admitted to our hospital ICU were included in this study. They were continuously observed for 72 hours to observe the presence of AKI. The urine and plasma samples were collected upon admission and at 6, 12, 24, 48, and 72 h after admission. The levels of plasma and urine biomarkers were determined by enzyme-linked immunosorbent assay (ELISA) and compared among groups. Furthermore, receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUCs) were calculated to evaluate the early diagnostic value of NGAL, KIM-l, and TIMP-2 in sepsis with AKI.

Results

Of 90 patients included, 38 (42.22%) were diagnosed to be complicated with AKI. In the AKI group, the levels of plasm and urine NGAL began to significantly increase at 6 h after admission (P<0.05) and reached the peak at 24 h (P<0.05). Compared with the non-AKI group, the AKI group had significantly higher levels of plasm and urine NGAL levels at 12, 24, 48, and 72 h (P<0.05). In the AKI group, the levels of urine KIM-1 and TIMP-2 began to significantly increase at 6 h after admission (P<0.05) and reached the peak at 12 h (P<0.05). Compared with the non-AKI group, the AKI group had significantly higher levels of urine KIM-1 and TIMP-2 at 12, 24, 48, and 72 h (P<0.05). ROC curve analysis showed that the AUCs of pNGAL, uNGAL, urinary KIM-1, and urinary TIMP-2 were 0.862, 0.858, 0.788, and 0.771, respectively, and the cutoff values were 119.30, 120.36, 90.07 and 3299.50 ng/L, respectively. ROC curve analysis at each time point showed that the AUCs of pNGAL, urine KIM-1, and urine TIMP-2 at 12 h were 1.00, 0.96 and 0.92, respectively, and the AUC of uNGAL at 18 h was 0.95.

Conclusion

Plasma and urine NGAL, KIM-1, and TIMP-2 increase markedly in early renal injury in septic patients complicated with AKI. Plasma and urine NGAL, KIM-1, and TIMP-2 can be used as diagnostic and predictive biomarkers for AKI in critically ill patients with sepsis.

Key words: Sepsis, Acute kidney injury, NGLA, KIM-1, TIMP-2

Haixia Wang, Hongbin Mou, Jiangquan Yu, Yuhuan Yang, Ruiqiang Zheng. Evaluation of NGAL, KIM-1, and TIMP-2 as early biomarkers in sepsis-associated acute kidney injury: a prospective clinical cohort study[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2019, 05(02): 120-126.

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URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2019.02.008

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References 22

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一般资料		AKI组（38例）	非AKI组（52例）	统计值	P值
性别［男性例数（%）］		17（44.7）	33（63.5）	χ²=3.118	0.090
年龄（岁，±s）		59.9±15.9	57.1±14.8	t=0.522	0.609
基础疾病		?	?	?	?
?	高血压	12（31.6）	13（25.0）	χ²=0.474	0.634
?	糖尿病	8（21.1）	20（38.5）	χ²=3.105	0.107
?	冠心病	5（13.1）	13（25）	χ²=1.924	0.192
?	COPD	8（21.1）	13（25）	χ²=0.191	0.802
?	肿瘤	7（18.4）	8（15.4）	χ²=0.146	0.778
APACHE Ⅱ评分（分，±s）		26.45±11.63	14.31±7.18	χ²=3.448	0.002
SOFA评分（分，±s）		5.61±3.23	2.82±2.67	t=1.837	0.083
入住ICU原因［例（%）］		?	?	?	?
?	肺部感染	15（39.5）	27（51.9）	χ²=1.367	0.288
?	腹腔感染	12（31.6）	17（32.7）	χ²=0.012	0.911
?	泌尿感染	0（0）	3（5.8）	χ²=2.268	0.260
?	其他部位感染	11（28.9）	5（9.6）	χ²=5.613	0.024
病死［例（%）］		18（47.4）	13（25.0）	χ²=4.865	0.043

一般资料		AKI组（38例）	非AKI组（52例）	统计值	P值
性别［男性例数（%）］		17（44.7）	33（63.5）	χ²=3.118	0.090
年龄（岁，±s）		59.9±15.9	57.1±14.8	t=0.522	0.609
基础疾病		?	?	?	?
?	高血压	12（31.6）	13（25.0）	χ²=0.474	0.634
?	糖尿病	8（21.1）	20（38.5）	χ²=3.105	0.107
?	冠心病	5（13.1）	13（25）	χ²=1.924	0.192
?	COPD	8（21.1）	13（25）	χ²=0.191	0.802
?	肿瘤	7（18.4）	8（15.4）	χ²=0.146	0.778
APACHE Ⅱ评分（分，±s）		26.45±11.63	14.31±7.18	χ²=3.448	0.002
SOFA评分（分，±s）		5.61±3.23	2.82±2.67	t=1.837	0.083
入住ICU原因［例（%）］		?	?	?	?
?	肺部感染	15（39.5）	27（51.9）	χ²=1.367	0.288
?	腹腔感染	12（31.6）	17（32.7）	χ²=0.012	0.911
?	泌尿感染	0（0）	3（5.8）	χ²=2.268	0.260
?	其他部位感染	11（28.9）	5（9.6）	χ²=5.613	0.024
病死［例（%）］		18（47.4）	13（25.0）	χ²=4.865	0.043

组别		例数	0 h	6 h	12 h	24 h	48 h	72 h	F值	P值
非AKI组		52	84.80±15.36	86.68±15.03	83.89±17.80	87.38±17.01	86.28±15.87	89.06±15.96	1.61	0.21
AKI组		38	86.94±19.95	92.54±19.73	112.48±22.35^a	158.74±41.85^a	170.18±46.87^a	168.58±43.63^a	7.56	0.00
?	t值	?	-1.32	-2.10	-1.89	-12.561	-12.03	-11.15	?	?
?	P值	?	0.23	0.08	0.06	0.00	0.00	0.00	?	?

组别		例数	0 h	6 h	12 h	24 h	48 h	72 h	F值	P值
非AKI组		52	84.80±15.36	86.68±15.03	83.89±17.80	87.38±17.01	86.28±15.87	89.06±15.96	1.61	0.21
AKI组		38	86.94±19.95	92.54±19.73	112.48±22.35^a	158.74±41.85^a	170.18±46.87^a	168.58±43.63^a	7.56	0.00
?	t值	?	-1.32	-2.10	-1.89	-12.561	-12.03	-11.15	?	?
?	P值	?	0.23	0.08	0.06	0.00	0.00	0.00	?	?

组别	pNGAL	uNGAL	尿KIM-1	尿TIMP-2
非AKI组（52例）	?	?	?	?
0 h	93.42±13.84	93.81±13.87	81.42±19.13	2604.98±907.55
6 h	99.10±15.20	97.80±16.72	83.65±15.22	3114.58±705.03
12 h	109.50±19.07	105.54±18.81	87.58±12.46	3168.61±873.37
24 h	107.35±20.29	102.04±19.17	84.69±14.83	3027.43±696.31
48 h	100.24±20.02	101.50±22.33	84.75±15.25	2966.13±664.24
72 h	95.52±13.69	104.76±21.09	81.02±15.03	2922.65±683.24
F值	1.81	0.37	0.06	1.32
P值	0.17	0.70	0.94	0.27
AKI组（38例）	?	?	?	?
0 h	94.53±15.14	85.74±10.85	86.70±11.43	2835.54±950.49
6 h	134.34±32.03^ab	151.47±25.90^ab	96.71±10.97^ab	4877.09±1639.60^ab
12 h	265.45±49.62^ab	325.92±96.25^ab	145.35±32.59^ab	5338.16±1421.41^ab
24 h	294.34±84.74^ab	334.82±128.24^ab	128.23±30.82^ab	5164.37±1777.82^ab
48 h	230.68±89.01^ab	235.05±97.04^ab	117.94±28.82^ab	4316.06±1364.40^ab
72 h	187.89±57.70^ab	159.37±41.83^ab	104.49±26.06^ab	3925.70±1349.54^ab
F值	5.31	7.11	4.89	8.25
P值	0.02	0.00	0.03	0.00

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