Urinary NGAL, IGFBP-7, and TIMP-2: novel biomarkers to predict contrast medium-induced acute kidney injury in children

Figures & data

Table 1. Patient demographics and clinical outcomes.

	CI-AKI group	Non CI-AKI group	Healthy controls group	p Value
Cases (n)	20	117	35
Gender (n, male/female)	13/7	64/53	19/16	0.678
Age (years)	1.76 (1.09–4.54)	3.2 (2.07–6.61)	2.20 (1.20–4.10)	0.058
BMI (kg/m^2)	15.89 (14.2–18.76)	15.19 (14.42–16.89)	15.35 (13.41–16.51)	0.334
Clinical basics n(%)
Thin	3 (15%)	18 (15.38%)	–	0.965
Obesity	3 (15%)	7 (5.98%)	–	0.152
Hypoalbuminemia	0	1 (0.85%)	–	0.687
Blood in the urinary	1 (5%)	14 (11.97%)	–	0.357
Proteinuria	1 (5%)	9 (8.41%)	–	0.669
Fever	5 (25%)	17 (15.88%)	–	0.119
Anemia	7 (35%)	26 (24.29%)	–	0.183
Surgery	16 (80%)	70 (59.82%)	–	0.085
Sepsis	2 (10%)	6 (5.13%)	–	0.282
Abnormal liver function	3 (15%)	9 (8.41%)	–	0.214
SCr
Baseline µmol/L	18.25 (12.83–22.25)	24.20 (21.00–33.00)*	21.40 (17.90–27.80)*	0.005
48–72 h after contrast administration µmol/L	25.10 (19.25–32.83)	25.00 (18.90–31.80)	–	0.831
Baseline
uNGAL ng/mL	27.69 (22.27–46.09)	27.37 (17.26–42.46)	23.49 (14.65–34.94)	0.315
uIGFBP-7 ng/mL	110.64 (78.53–156.84)	140.72 (112.50–161.66)	125.28 (113.61–141.91)	0.052
uTIMP-2 ng/mL	1.97 (1.55–2.75)	2.13 (1.46–2.51)	1.99 (1.82–2.34)	0.932
[uIGFBP-7]*[uTIMP-2] (ng/mL)^2/1000	0.206 (0.186–0.294)	0.261 (0.202–0.359)	0.247 (0.199–0.321)	0.251

CI-AK: Contrast medium-induced acute kidney injury; BMI: Body Mass Index; uNGAL: neutrophil gelatinase-associated lipocalin; uIGFBP-7: insulin like growth factor binding protein-7; uTIMP-2: tissue inhibitor of metalloproteinase-2.

*p < 0.05 vs. CI-AKI group.

Table 2. Comparison of the change of urinary biomarkers at time after injection of CM.

	CI-AKI group	Non CI-AKI group	p Value
uNGAL ng/mL
Baseline	27.69 (22.27–46.09)	27.37 (17.26–42.46)	0.674
2 h	51.74 (30.41–97.81)**	28.98 (19.16–43.11)	0.002
6 h	45.33 (27.99–68.89)**	28.42 (19.84–44.35)	0.007
12 h	35.48 (25.59–53.89)*	29.72 (17.24–48.57)	0.114
24 h	33.97 (26.27–48.32)	27.49 (17.13–45.57)	0.216
48 h	28.11 (19.71–37.32)	26.39 (17.39–44.39)	0.756
p Value	<0.001	0.356
uIGFBP-7 ng/mL
Baseline	110.64 (78.53–156.84)	140.72 (112.50–161.66)	0.079
2 h	151.68 (126.92–183.52)**	141.09 (117.21–167.20)	0.128
6 h	197.34 (154.36–249.62)**	138.74 (112.11–162.78)	<0.001
12 h	140.86 (111.38–185.09)**	136.33 (105.72–164.29)	0.262
24 h	117.16 (97.51–161.56)	135.48 (111.13–161.15)	0.205
48 h	126.09 (100.98–173.53)	132.69 (108.49–153.89)	0.814
p Value	<0.001	0.117
uTIMP-2 ng/mL
Baseline	1.97 (1.55–2.75)	2.13 (1.46–2.51)	0.791
2 h	2.26 (1.90–4.03)**	2.28 (1.60–2.68))**	0.088
6 h	3.98 (2.49–5.59)**	2.15 (1.46–2.73)	<0.001
12 h	2.38 (1.68–2.81)	2.20 (1.55–2.61)	0.357
24 h	2.07 (1.66–2.54)	2.07 (1.36–2.54)	0.705
48 h	1.77 (1.39–2.83)	2.10 (1.39–2.57)	0.833
p Value	<0.001	0.035
[uIGFBP-7]*[uTIMP-2] (ng/mL)^2/1000
Baseline	0.206 (0.186–0.294)	0.261 (0.202–0.359)	0.128
2 h	0.377 (0.301–0.539)**	0.287 (0.235–0.386)**	0.003
6 h	0.833 (0.458–1.321)**	0.259 (0.201–0.376)	<0.001
12 h	0.287 (0.222–0.456)**	0.266 (0.191–0.363)	0.207
24 h	0.226 (0.189–0.298)	0.252 (0.177–0.381)	0.661
48 h	0.228 (0.194–0.335)	0.254 (0.175–0.337)	0.951
p Value	<0.001	0.012

uNGAL: Neutrophil gelatinase-associated lipocalin; uIGFBP-7: insulin like growth factor binding protein-7; uTIMP-2: tissue inhibitor of metalloproteinase-2.

*p < 0.05, **p < 0.01 vs. baseline.

Table 3. Performance of uNGAL, uIGFBP-7, uTIMP-2, and [uIGFBP-7]*[uTIMP-2] for the diagnosis of CI-AKI.

	uNGAL	uIGFBP-7	uTIMP-2	[uIGFBP-7]* [uTIMP-2]
AUC	0.718	0.779	0.779	0.811
95% CI	0.575–0.860	0.658–0.901	0.650–0.908	0.681–0.941
Cutoff value	36.274	153.061	2.951	0.417
Sensitivity (%)	0.70	0.80	0.75	0.80
Specificity (%)	0.684	0.667	0.821	0.812

Figure 1. Non CI-AKI group and CI-AKI group the level of uNGAL, uIGFBP-7, uTIMP-2, and [uIGFBP-7]*[uTIMP-2] at 2 h, 6 h.

Data availability statement

The raw data supporting the conclusions of this manuscript will be made available by the authors, the datasets during the current study are available in the website of http://www.chictr.org.cn/login.aspx?referurl=%2faddproject2.aspx

Figure 1. Non CI-AKI group and CI-AKI group the level of uNGAL, uIGFBP-7, uTIMP-2, and [uIGFBP-7]*[uTIMP-2] at 2 h, 6 h.