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Aging and disease    2018, Vol. 9 Issue (2) : 182-191     DOI: 10.14336/AD.2017.0307
Orginal Article |
Urinary Neutrophil Gelatinase-Associated Lipocalin Is Excellent Predictor of Acute Kidney Injury in Septic Elderly Patients
da Rocha Erica Pires, Yokota Lais Gabriela, Sampaio Beatriz Motta, Cardoso Eid Karina Zanchetta, Dias Dayana Bitencourt, de Freitas Fernanda Moreira, Balbi Andre Luis, Ponce Daniela*
University Sao Paulo State-UNESP, Distrito de Rubiao Junior, without number, Botucatu, Sao Paulo, Brazil
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Abstract  

Elderly is the main age group affected by acute kidney injury (AKI). There are no studies that investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic elderly population. This study aimed to evaluate the efficacy of uNGAL as predictor of AKI diagnosis and prognosis in elderly septic patients admitted to ICUs. We prospectively studied elderly patients with sepsis admitted to ICUs from October 2014 to November 2015. Assessment of renal function was performed daily by serum creatinine and urine output. The level of uNGAL was performed within the first 48 hours of the diagnosis of sepsis (NGAL1) and between 48 and 96 hours (NGAL2). The results were presented using descriptive statistics and area under the receiver operating characteristic curve (AUC-ROC) and p value was 5%. Seventy-five patients were included, 47 (62.7%) developed AKI. At logistic regression, chronic kidney disease and low mean blood pressure at admission were identified as factors associated with AKI (OR=0.05, CI=0.01-0.60, p=0.045 and OR=0.81, CI=0,13-0.47; p=0.047). The uNGAL was excellent predictor of AKI diagnosis (AUC-ROC >0.95, and sensitivity and specificity>0.89), anticipating the AKI diagnosis in 2.1±0.3 days. Factors associated with mortality in the logistic regression were presence of AKI (OR=2.14, CI=1.42-3.98, p=0.04), chronic obstructive pulmonary disease (OR = 9.37, CI =1.79-49.1, p=0.008) and vasoactive drugs (OR=2.06, CI=0.98-1.02, p=0.04). The accuracy of NGALu 1 and 2 as predictors of death was intermediate, with AUC-ROC of 0.61 and 0.62; sensitivity between 0.65 and 0.77 and specificity lower than 0.6. The uNGAL was excellent predictor of AKI in septic elderly patients in ICUs and can anticipate the diagnosis of AKI in 2.1 days.

Keywords elderly      acute kidney injury      biomarker      NGAL     
Corresponding Authors: Ponce Daniela   
About author:

These authors contributed equally to this work.

Issue Date: 01 April 2018
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da Rocha Erica Pires
Yokota Lais Gabriela
Sampaio Beatriz Motta
Cardoso Eid Karina Zanchetta
Dias Dayana Bitencourt
de Freitas Fernanda Moreira
Balbi Andre Luis
Ponce Daniela
Cite this article:   
da Rocha Erica Pires,Yokota Lais Gabriela,Sampaio Beatriz Motta, et al. Urinary Neutrophil Gelatinase-Associated Lipocalin Is Excellent Predictor of Acute Kidney Injury in Septic Elderly Patients[J]. Aging and disease, 2018, 9(2): 182-191.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.0307     OR     http://www.aginganddisease.org/EN/Y2018/V9/I2/182
CharacteristicsSeptic elderly patients
N=75
Non-AKI patients
N= 28
AKI patients
N= 47
p
Age (years)71.4±7.571.7 ±7.671.3±7.60.82
Male sex n (%)39 (52)12 (42,9)27 (57,4)0.22
Baseline creatinine1.16±0.520.8±0.31.3±0.30.0009
Comorbidities n (%)
 Hypertension45 (60)15 (53,5)30 (63.8)0.38
 Diabetes25 (33.3)7 (25)18 (38.3)0.23
 CVC disease35 (46.7)11 (39.3)24 (51.1)0.32
 CKD34 (49.3)4 (17.4)30 (63.8)0.0002
 COPD17 (22.7)8 (28.6)9 (19.1)0.34
Mechanical ventilation n (%)49 (65.3)16 (57.1)33 (70.2)0.25
Noradrenaline use n (%)59 (78.7)19 (67.9)40 (85.1)0.07
Infection Focus n (%):0.36
 Lung39 (52)12(42.8)27 (57.4)
 Urine18 (24)10 (35.7)8 (17.0)
 abdominal7 (9,3)2 (7.1)5 (10.6)
Urine output in 24h (ml)874.2±729.7797.8±535.6919.2±826.40.52
APACHE II17.7±6.814±4.819.4±7.00.0045
Temperature36.8±1.136.4±0.937.1±1.10.007
Outcome n (%):0.03
 discharge35 (46.7)18 (64.2)17 (36.2)
 death40 (53.3)10 (35.7)30 (63.8)
Table 1  Patients demographics and clinical characteristics (n=75).
Figure 1.  Screening and enrollment.
CharacteristicsNon-Survivors
(N=40)
Survivors
(N=35)
p
Male sex n (%)22 (55)17 (48.6)0.57
Age (years)70.9±7.2672±7.90.53
MBP78.4±22.389.3±21.80.03
Comorbidities n (%)
 Hypertension24 (60)21 (60)1.0
 Diabetes13 (32.5)12 (34.3)0.87
 Dyslipidemia6 (15)10 (28.6)0.15
 Cardiovascular disease19 (47.5)16 (45.7)0.87
 Liver disease4(10)00.05
 CKD19 (47.5)15 (42.8)0.71
 COPD12 (34.3)10 (28.7)0.02
Baseline creatinine1.2±0.51.0±0.40.13
Noradrenaline use n (%)36 (90)23 (65.7)0.01
Mechanical ventilation n (%)29 (72.5)20 (57.1)0.16
Urine output in 24h (ml)842.6±414.2912.5±624.30.70
Focus n (%):0.81
 lung20 (50)19(54.3)
 urine11(27.5)7(20)
APACHE II19.7±6.615.1±6.50.009
AKI28 (70)15 (42.9)0.03
KDIGO n (%):
 I6 (20.7)8 (53.3)0.02
 II7 (25)4 (26.6)
 III15 (53.6)3 (20)
Need for dialysis n (%)3 (7.5)2 (5.7)0.63
Table 2  Patients demographics and clinical characteristics (n=75) according to outcome.
Figure 2.  ROC analysis of uNGAL in septic elderly patients with AKI vs non-AKI. A) ROC analysis of uNGAL measured on first 48 hours of admission to ICU in septic elderly patients with AKI vs non-AKI. B) ROC analysis of uNGAL measured between 48-96 hours of admission to ICU in septic elderly patients with AKI vs non-AKI. C) ROC analysis of uNGAL/uCr measured on first 48 hours of admission to ICU in septic elderly patients with AKI vs non-AKI. D) ROC analysis of uNGAL/uCr measured between 48-96 hours of admission to ICU in septic elderly patients with AKI vs non-AKI.
AKIORCI (95%)p
CKD0.05(0.01 -0.60)0.04
Temperature1.84(0.34 - 9.81)0.71
MBP0.81(0.13 - 090)0.04
DeathORCI (95%)p
Noradrenaline use2.06(1.14 - 1.63)0.04
Mechanical ventilation0.38(0.07- 1.94)0.24
COPD9.37(1.79 - 49.10)0.008
CKD0.39(0.08 - 1.73)0.21
AKI2.14(1.42 - 3.98)0.04
Table 3  Multivariable analysis for AKI and death risk (n=75).
Non-AKI
N=28
AKI
N=47
p
uNGAL (ng/ml)
at moment 1 (<48h)*6.8±3.719.1±4.6<0.0001
at moment 2 (48-96h)6.1±4.019.6±5.6<0.0001
uNGAL /uCr (ng/mg):
at moment 1 (<48h)56.6±39.9127.9±30.6<0.0001
at moment 2 (48-96h)58.8±43.4138.3±31.5<0.0001
Table 4  Urinary NGAL values according to presence of acute kidney injury.
Non-survivors
N=35
Survivors
N=40
p
uNGAL (ng/ml)
at moment 1 (<48h*)15.9±7.312.9±7.20.08
at moment 2 (48-96h)15.9±813.0± 8.30.13
uNGAL /uCr (ng/mg)
at moment 1 (<48h)113.9 ±47.286.9±27.7<0.001
at moment 2 (48-96h)122.3±50.893± 51.70.19
Table 5  Urinary NGAL values according to patient outcome.
Figure 3.  ROC analysis of uNGAL in survivors versus non-survivor’s septic elderly patients. A) ROC analysis of uNGAL measured on first 48 hours of admission to ICU in survivors versus non-survivor’s septic elderly patients. B) ROC analysis of uNGAL measured between 48-96 hours of admission to ICU in survivors versus non-survivor’s septic elderly patients. C) ROC analysis of uNGAL/uCr measured on first 48 hours of admission to ICU in survivors versus non-survivor’s septic elderly patients. D) ROC analysis of uNGAL/uCr measured between 48-96 hours of admission to ICU in survivors versus non-survivor’s septic elderly patients
AUC-ROCpcutoffSensitivitySpecificityCI (95%)
uNGAL10.970.0113.391.592.9(0.64-0.81)
uNGAL20.960.0112.791.589.7(0.55-0.82)
uNGAL/uCr10.890.0489.989.489.6(0.68-0.83)
uNGAL/uCr20.890.00196.789.489.7(0.63-0.91)
Table 6  Urinary NGAL sensitivity and specificity in septic elderly AKI patients (n=47).
AUC-ROCpcutoffSensitivitySpecificityCI (95%)
uNGAL10.610.0112.2171.554.3(0.48-0.73)
uNGAL20.620.0113,.2965.051.4(0.47-0.72)
uNGAL/uCr10.670.0469.3977.557.1(0.54-0.79)
uNGAL/uCr20.670.001111.2067.545.7(0.58-0.78)
Table 7  Urinary NGAL sensitivity and specificity in non-survival septic patients (n=35).
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