Serum NGAL and FGF23 may have certain value in early diagnosis of CIN

Figures & data

Table 1. Baseline demographic and clinical characteristics.

Variable	CIN		p
	No (n = 172)	Yes (n = 30)
Age, years	59.58 ± 10.79	62.56 ± 8.54	.187
Male, n (%)	141 (82%)	24 (80%)	.796
Body mass index, kg/m^2	23.85 (21.80,25.21)	24.06 (22.49,26.02)	.544
Current smokers, n (%)	82 (48%)	14 (47%)	.919
Hypertension, n (%)	107 (62%)	18 (60%)	.818
DM, n (%)	37 (22%)	12 (40%)	.036
CKD, n (%)	11 (6.4%)	6 (20.0%)	.043
Cardiac function levels III–IV, n (%)	33 (19%)	4 (13%)	.807
Prior PCI, n (%)	23 (13%)	2 (7%)	.466
Prior myocardial infarction, n (%)	24 (14%)	3 (10%)	.767
Systolic blood pressure, mmHg	129.42 ± 21.69	139.30 ± 22.29	.023
Diastolic blood pressure, mmHg	77.58 ± 12.44	80.17 ± 14.48	.306
Left ventricular diameter, mm	51.63 ± 5.94	50.32 ± 10.25	.416
Urine output within 24 h after PCI, ml PCIlml	1530 (1200,2130)	1480 (1240,2100)	.647
Prehospital medications, n (%)
Aspirin	119 (69.1%)	15 (50.0%)	.065
ß-blocker	73 (42.4%)	7 (23.3%)	.076
Calcium channel blocker	40 (23.3%)	5 (16.7%)	.574
ACEI/ARB	61 (35.5%)	7 (23.3%)	.277
Statins	90 (34.9%)	6 (20.0%)	.002

Definitions: Current smokers were those who smoke daily at the last 6 months. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, at least two measurements, or the use of antihypertensive drugs. DM was defined as fasting blood glucose ≥7.0 mmol/L, or random blood glucose ≥11.1 mmol/L, at least two measurements, or the use of antidiabetes drugs. CKD was defined as eGFR <60 mL/min or abnormal urine elements more than 3 months. Bold number p < .05.

Table 2. Laboratory data.

Variable	CIN		p
	No (n = 172)	Yes (n = 30)
White blood cell, *10^9/L	7.76 ± 2.52	7.88 ± 2.21	.794
Platelet, *10^9/L	207.57 ± 66.37	212.93 ± 62.19	.668
Hemoglobin, g/L	133.80 ± 16.40	131.20 ± 19.30	.470
Fasting plasma glucose, mmol/L	5.18 (4.74,6.34)	5.98 (4.90,7.22)	.078
SCr, umol/L	95.3 (85.0,108.0)	96.6 (87.6,112.0)	.124
eGFR, ml/min/1.73 m^2	88.20 (75.69,100.93)	87.30 (74.00,101.28)	.197
Uric acid, umol/L	373.16 ± 97.53	367.10 ± 105.30	.217
Blood urea nitrogen, mmol/L	5.47 ± 1.66	5.45 ± 1.39	.934
Cystatin-C, mg/L	0.82 (0.71,1.02)	0.83 (0.76,1.04)	.199
Triglyceride, mmol/L	1.64 (1.21,2.42)	2.18 (1.15,3.11)	.189
Total cholesterol, mmol/L	4.29 (3.63,5.19)	5.05 (4.21,5.44)	.066
HDL, mmol/L	1.12 ± 0.28	1.10 ± 0.28	.643
LDL, mmol/L	2.80 ± 0.95	3.16 ± 0.97	.062
hsCRP, mg/L	2.78 (0.70,12.57)	3.13 (1.56,26.44)	.247
Fibrinogen, g/L	3.25 (2.71,3.96)	3.11 (2.73,3.81)	.659
Lactic dehydrogenase, U/L	210.0 (172.4,357.5)	220.0 (179.2,411.0)	.449
Creatine kinase, U/L	96.25 (67.95,222.80)	94.60 (68.25,232.40)	.873
Creatine kinase isoenzyme, U/L	19.90 (15.13,32.48)	18.60 (13.45,26.05)	.567
Myohemoglobin, ug/L	32.65 (24.43,44.80)	31.50 (22.05,69.65)	.806

Abbreviations: eGFR: estimated glomerular filtration rate, it was assessed by modified Modification of Diet in Renal Disease (MDRD) equations. HDL: high-density lipoprotein cholesterol. LDL: low-density lipoprotein cholesterol. hsCRP: high sensitivity C-reactive protein.

Table 3. Angiographic characteristics.

Variable	CIN		p
	No (n = 172)	Yes (n = 30)
Type of contrast			.296
Iohexol	76 (42.9%)	11 (36.7%)
Iodixanol	56 (32.6%)	8 (26.7%)
Iopromide	40 (23.3%)	11 (36.7%)
Contrast volume, mL	150 (120, 162.5)	160 (137.5,190)	.041
Number of stents used			.132
1, n (%)	56 (32.6%)	14 (46.7%)
2, n (%)	64 (37.2%)	5 (16.7%)
3, n (%)	45 (26.2%)	10 (33.3%)
4, n (%)	7 (4.1%)	1 (3.3%)
Gensini score	80 (59,107.5)	82.5 (63,114.25)	.533

Definition: Gensini score is a scoring system for determining the severity of CHD, which depends on the degree of luminal narrowing and the geographical importance of its location. Bold number p < .05.

Table 4. Serum levels of SCr, NGAL, and FGF23.

	Non-CIN group (n = 172)	CIN group (n = 30)
SCr (umol/L)
Baseline	95.3 (85, 108)	96.6 (87.6, 112)
1 day after PCI	96.4 (86.3, 108.7)	97.2 (88.2, 116.4)
2 days after PCI	98.0 (87.5, 111.0)**	110.65 (101.2, 143.5)**##
3 days after PCI	100 (89.1, 111.2)**	113.3 (104.1, 155.8)**##
eGFR(ml/min/1.73m^2)
Baseline	88.20 (75.69, 100.93)	87.30 (74.00, 101.28)
1 day after PCI	87.49 (75.02, 99.94)	86.72 (73.85, 100.26)
2 days after PCI	85.56 (74.19, 97.32)**	75.34 (58.73, 85.21)**##
3 days after PCI	83.97 (72.82, 95.37)**	70.70 (50.71, 79.04)**##
Serum NGAL (ng/mL)
Baseline	90 (77, 111.75)	88 (75, 108.5)
0 h after PCI	92.5 (77, 110)	89 (76.75, 111)
1 day after PCI	100.5 (86, 123)**	140.5 (119, 164.5)**##
2 days after PCI	93.5 (79, 111.75)	116.5 (91.5, 152)**##
Serum FGF23 (ng/L)
Baseline	108.32 (94.46, 125.28)	111.75 (85.13, 138.68)
0 h after PCI	112.54 (95.56, 128.62)	113.4 (87.32, 143.84)
1 day after PCI	115.78 (99.29, 136.47)**	140.93 (108.32, 175.63)**##
2 days after PCI	112.96 (97.34, 128.95)	123.55 (94.58, 151.94)**

** p < .01 versus baseline. ##p < .01 compared among groups at the same time.

Figure 1. ROC curve of serum NGAL and FGF23, increment percentage between 1 day after PCI and baseline (A), absolute value 1 day after PCI (B). **p < .01.

Table 5. Diagnostic characteristics of serum NGAL and FGF23 for CIN.

	AUC (95% CI)	Cut point	Sensitivity (%)	Specificity (%)
Serum NGAL
Increment percentage	0.899 (0.834-0.964)	49%	80.0	92.4
Absolute value after 1 day	0.779 (0.675-0.882)	111.50 (ng/mL)	86.7	63.0
Serum FGF23
Increment percentage	0.814 (0.733-0.894)	20%	73.3	87.6
Absolute value after 1 day	0.643 (0.520–0.766)	139.22 (ng/L)	50.0	80.6

Figure 2. Correlation between SCr and serum NGAL (A), between eGFR and serum NGAL (B), between SCr and serum FGF23 (C), between eGFR and serum FGF23 (D).

Figure 3. A-G: Shown are clinical models from models A–G.

Table 6. Clinical models.

	Model A	Model B	Model C	Model D	Model E	Model F	Model G
Constant	–12.778	–11.502	–19.947	–7.518	–6.614	–10.514	–4.120
X1	1.050	0.826	1.162	1.015	0.776	1.084	0.787
X2	0.974	1.071	0.932	0.443	0.819	0.317	0.953
X3	0.020	0.020	0.020	0.020	0.018	0.020	0.019
X4	–0.838	–1.270	–0.842	–1.119	–1.190	–1.130	–1.361
X5	6.115		5.566
X6		6.123	6.674
X7				0.026		0.027
X8					0.024	0.027

X1-X8: DM, CKD, SBP, statins, increment percentage of serum NGAL, increment percentage of serum FGF23, serum NGAL after 1 day, serum FGF23 after 1 day, respectively.