Serum uric acid may predict development of progressive acute kidney injury after open heart surgery

Figures & data

Table 1. General characteristics* of the whole study cohort.

	Non-AKI (n = 20)	Nonprogressed AKI (n = 20)	Progressed AKI (n = 20)	p Value**
Age, years	51.8 (16.6)	56.7 (15.1)	61.7 (9.6)^a	0.132
Gender, male	15 (75%)	12 (60%)	15 (75%)	0.793
Comorbidities
Coronary artery disease	15 (75%)	15 (75%)	18 (90%)	0.392
Diabetes mellitus	5 (25%)	7 (35%)	6 (30%)	0.788
Hypertension	8 (40%)	8 (40%)	13 (65%)	0.189
History of myocardial infarction	4 (20%)	3 (15%)	5 (25%)	0.732
Pervious cardiac surgery	1 (5%)	3 (15%)	2 (10%)	0.574
Chronic heart failure	–	1 (5%)	5 (25%)	0.020
Peripheral vascular disease	2 (10%)	3 (15%)	5 (25%)	0.432
COPD	3 (15%)	4 (20%)	5 (25%)	0.732
Cardiac function
Systolic blood pressure, mmHg	117.3 (11.0)	121.3 (7.4)	117.4 (14.3)	0.514
Diastolic blood pressure, mmHg	69.3 (4.58)	75.3 (6.4)^a	71.4 (10.2)	0.026
Left ventricle ejection function, %	53.8 (8.26)	55.9 (9.7)	51.1 (11.0)	0.485
Renal function
Urea, mg/dL	31.7 (10.2)	33.6 (10.6)	47.1 (21.5)^a,b	0.010
Creatinine, mg/dL	0.75 (0.13)	0.80 (0.25)	0.98 (0.34)^a	0.048
eGFR, mL/min	113.7 (23.6)	107.3 (37.1)	88.4 (38.5)^a	0.014
Pre-operative biomarkers
Serum NGAL, ng/mL	102.0 (51.5)	105.4 (44.8)	140.8 (67.9)^a,b	0.001
Urine NGAL, ng/mL	2.4 (9.3)	4.1 (9.78)	7.86 (12.7)	0.455
Serum uric acid, mg/dL	5.3 (1.27)	4.95 (2.73)	6.2 (2.6)	0.103
Biochemistry
Albumin, g/dL	4.02 (0.19)	4.14 (0.28)	3.89 (0.45)	0.293
Hemoglobin, g/dL	12.5 (2.27)	11.5 (1.82)	11.1 (1.47)^a	0.096
Hematocrit, %	37.9 (5.84)	35.6 (5.07)	34.9 (4.39)	0.215
White blood cells	7.99 (2.67)	5.52 (1.54)^a	7.50 (2.83)^b	0.005
Platelets	229.4 (43.4)	194.2 (60.5)	202.4 (97.0)	0.149
Type of surgery				0.567
CABG	12 (60%)	12 (85%)	14 (45%)	–
Valves	8 (40%)	6 (30%)	5 (25%)	–
CABG + Valves	–	2 (10%)	1 (5%)	–
On-Pump (CPB)	15 (75%)	17 (85%)	16 (80%)	0.732
CPB time. min	107.6 (36.2)	122.2 (38.6)	115.4 (35.8)	0.360
Aortic-cross clamp time, min	59.0 (18.6)	75.4 (35.6)	75.2 (35.7)	0.208
Outcome
Stage I AKI	–	19 (95%)	–	–
Stage II AKI	–	1 (5%)	6 (30%)	–
Stage III AKI	–	–	14 (70%)	–
Renal replacement therapy	–	–	7 (35%)	–
Sepsis	1 (5%)	–	2 (10%)	–
Exitus	–	–	4 (20%)	–
Post-operative length of stay
Intensive care unit	2.5 (1.0)	2.95 (1.15)	8.35 (8.22)^a,b	0.001
Surgical ward	4.60 (1.35)	5.85 (2.48)	5.44 (2.90)	0.242
Total length of stay	10.9 (3.19)	12.1 (4.84)	16.3 (8.11)^a	0.062

Notes: COPD – chronic obstructive pulmonary disease; eGFR – estimated glomerular filtration rate; CABG – coronary artery bypass grafting; CPB – cardio-pulmonary bypass; NGAL – serum neutrophil gelatinase associated lipocalin; AKI – acute kidney injury.

*Pre-operative values; Values presented as mean (SD), median (IQR) or number (%).

**Kruskal–Wallis test and Chi-square test.

^aCompared with non-AKI group (p ≤ 0.05, Mann–Whitney U-test).

^bCompared with non-progressed AKI group (p ≤ 0.05, Mann–Whitney U-test).

Figure 1. Changes in sNGAL, uNGAL, serum creatinine, and uric acid levels after cardiac surgery in non-AKI, non-progressing AKI, and progressing AKI groups.

Figure 2. ROC curves showing cut-off points and AUC for 2nd (Panel A) and 24th hour (Panel B) levels of sNGAL, uNGAL, and serum uric acid to predict progressing AKI. Notes: AUC – Area under the ROC curve; ROC – receiver operator characteristics. *Compared by the method of DeLong et al.

Table 2. Second hour markers to predict AKI defined/persisted at 12th, 24th, and 48th hours and requirement of CRRT.

	Cut-off	Spec. (%)	Sens. (%)	PPV (%)	NPV (%)	AUC* (95% CI)	p Value**
AKI at 12 h
sNGAL	199.0	73.1	52.4	68.2	59.4	0.649 (0.507–0.774)	0.0482
uNGAL	11.85	50.0	89.3	65.8	81.3	0.683 (0.542–0.803)	0.0140
Uric acid	6.06	92.3	40.7	76.5	95.5	0.639 (0.497–0.766)	0.0716
Creatinine	1.26	92.3	37.8	84.6	58.5	0.630 (0.488–0.758)	0.0970
AKI at 24 h
sNGAL	175.4	46.4	79.3	58.3	72.2	0.646 (0.504–0.772)	0.0561
uNGAL	27.1	82.1	63.7	77.3	71.9	0.705 (0.565–0.821)	0.0066
Uric acid	5.45	75.0	64.1	70.8	70.0	0.725 (0.586–0.837)	0.0013
Creatinine	1.0	78.6	63.9	73.9	71.0	0.761 (0.625–0.866)	0.0001
AKI at 48 h
sNGAL	198.8	66.7	53.9	45.0	75.0	0.551 (0.392–0.710)	0.5352
uNGAL	43.3	27.8	98.5	40.9	100.0	0.461 (0.304–0.618)	0.6343
Uric acid	5.75	86.1	70.7	72.2	86.1	0.769 (0.610–0.929)	0.0012
Creatinine	0.90	66.7	76.1	53.8	85.7	0.743 (0.590–0.896)	0.0022
RRT
sNGAL	168.1	73.5	3.1	0.0	87.8	0.520 (0.380–0.658)	0.8573
uNGAL	5.91	93.9	58.1	50.0	95.8	0.722 (0.584–0.836)	0.1496
Uric acid	5.60	65.3	98.7	22.7	100.0	0.782 (0.648–0.883)	0.0002
Creatinine	1.54	98.0	38.8	66.7	94.1	0.651 (0.509–0.776)	0.3391

Notes: Spec – specificity; Sens – sensitivity; PPV – positive predictive value; NPV – negative predictive value; AUC – area under the curve; AKI – acute kidney injury.

*AUC compared by the method of DeLong et al.16

**Significance level p (Null hypothesis: true area = 0.5).

Table 3. Multivariate analysis of 2nd hour markers to predict AKI incidence.

	B	S.E.	Wald	p Value	Exp(B)
For all cases of AKI
Constant	−2.877	1.256	5.246	0.022	0.056
Creatinine at 2 h	3.039	1.371	4.914	0.027	20.89
For progressing AKI
Constant	−5.161	1.608	10.298	0.001	0.006
uNGAL at 2 h	0.036	0.017	4.705	0.030	1.037
Uric acid at 2 h	0.617	0.251	6.041	0.014	1.853

Notes: Logistic regression analysis with backward stepwise (Conditional method). Variables entered on step 1: sNGAL, uNGAL, serum creatinine, and serum uric acid at 2 h. Model was finished at step 3.

DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics. 1988;44(3):837–845

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