• Childhood Kidney Diseases
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• v.19 no.2
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• pp.79-88
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• 2015

Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as one of the most promising biomarkers of renal epithelial injury. Numerous studies have presented the diagnostic and prognostic utility of urinary and plasma NGAL in patients with acute kidney injury, chronic kidney disease, renal injury after kidney transplantation, and other renal diseases. NGAL is a member of the lipocalin family that is abundantly expressed in neutrophils and monocytes/macrophages and is a mediator of the innate immune response. The biological significance of NGAL to hamper bacterial growth by sequestering iron-binding siderophores has been studied in a knock-out mouse model. Besides neutrophils, NGAL is detectable in most tissues normally encountered by microorganisms, and its expression is upregulated in epithelial cells during inflammation. A growing number of studies have supported the clinical utility of NAGL for detecting invasive bacterial infections. Several investigators including our group have reported that measuring NGAL can be used to help predict and manage urinary tract infections and acute pyelonephritis. This article summarizes the biology and pathophysiology of NGAL and reviews studies on the implications of NGAL in various renal diseases from acute kidney injury to acute pyelonephritis.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.524-529
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• 2018

Background: An increase in neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular injury. Diabetic nephropathy causes typical changes in the kidney, characterized by glomerulosclerosis and eventual tubular damage. We validated the usefulness of plasma NGAL (pNGAL) as a biomarker of tubular damage in patients with diabetic nephropathy. Methods: We included 376 patients with diabetes mellitus (260 patients with chronic renal insufficiency who had not received hemodialysis and 116 hemodialyzed due to diabetic nephropathy) and 24 healthy controls. Patients with chronic renal insufficiency were divided into three groups according to urinary albumin excretion (UAE) levels. pNGAL levels were measured using the Triage NGAL test (Alere, San Diego, CA, USA) and were compared between groups. We also examined whether pNGAL level was related to the degree of albuminuria and cystatin C-based glomerular filtration rate (GFR). Results: Mean pNGAL levels of the healthy controls, chronic renal insufficiency patients with diabetes mellitus, and hemodialyzed patients were $61.9{\pm}5.3ng/mL$, $93.4{\pm}71.8ng/mL$, and $1,536.9{\pm}554.9ng/mL$, respectively. pNGAL level increased significantly in patients with severe albuminuria (P <0.001) and had a moderate correlation with the degree of albuminuria (r=0.467; P <0.001) and GFR (r=0.519; P <0.001). Multivariate regression analysis showed that the pNGAL level was associated with tubular damage independent of patient age, sex, and GFR. Conclusions: pNGAL level independently reflects the degree of tubular damage in patients with diabetic nephropathy. Measurement of pNGAL, combined with UAE, would enable simultaneous, highly reliable assessments of tubular damage for such patients.

• Clinical and Experimental Pediatrics
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• v.64 no.7
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• pp.347-354
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• 2021

Background: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a valuable biomarker of urinary tract infection (UTI) in children. Purpose: This study aimed to compare the diagnostic accuracy of urinary NGAL (uNGAL) with those of serum C-reactive protein (CRP) and white blood cell (WBC) count for predicting UTI and acute pyelonephritis (APN) in febrile children. Methods: The medical charts of children undergoing uNGAL measurements between November 2017 and August 2019 were retrospectively reviewed. Patients with a suspected or diagnosed UTIs were included. The diagnostic accuracies of uNGAL, serum CRP, and WBC count for detecting UTI and APN were investigated. Independent predictors of UTI and APN were investigated using multivariable logistic regression analyses. Results: A total of 321 children were enrolled in this study. The uNGAL levels were higher in the UTI group (n=157) than in the non-UTI group (n=164) (P<0.05). Among children with a UTI, uNGAL levels were higher in the APN group (n=70) than, the non-APN group (n=87) (P<0.05). In the multivariate analysis, uNGAL was independently associated with UTI and APN (both P<0.05). Serum CRP and WBC count were not correlated with the presence of UTI and APN. Receiver operating curve analyses showed that the uNGAL level had the highest area under the curve (AUC) for predicting UTI and APN, respectively (AUC, uNGAL vs. CRP vs. WBC count, 0.860 vs. 0.608 vs. 0.669 for UTI; 0.780 vs. 0.680 vs. 0.639 for APN, all P<0.05, respectively). The predictive values and likelihood ratios of uNGAL were superior to those of serum CRP and WBC count for detecting UTI and APN at each cutoff level. Conclusion: UNGAL may be more useful than serum CRP and WBC count for identifying and assessing UTI in febrile children.

• Childhood Kidney Diseases
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• v.24 no.2
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• pp.83-90
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• 2020

Purpose: To investigate the association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and leukocyte differential count in children with urinary tract infections (UTIs). Methods: A retrospective chart review was performed in children undergoing uNGAL measurements between June 2018 and September 2019. Patients with suspected or diagnosed UTIs were included. The relationship between uNGAL and blood leukocyte differential count was investigated in children. Results: A total of 197 children were included in this study, 119 of whom (60%) had UTIs. The non-UTI patients (n=78) were diagnosed with pneumonia, acute gastroenteritis, viral upper respiratory infection, and others. After adjusting for age, gender, and fever duration, the leukocyte count, monocyte count, and uNGAL levels were higher in the UTI group than in the non-UTI group (P<0.05). uNGAL showed positive correlations with neutrophil counts, monocyte counts, the neutrophil-to-lymphocyte ratio, and the monocyte-to-lymphocyte ratio in the UTI group (P<0.05). uNGAL levels were only associated with the neutrophil-to-lymphocyte ratio in the non-UTI group (P<0.05). In a multivariable logistic regression analysis, only uNGAL was associated with the presence of UTI (P<0.05). The area under the receiver operating characteristic curves for uNGAL and monocyte counts to identify UTI were 0.89 (95% confidence interval (CI): 0.824-0.939; P=0.025) and 0.7 (95% CI: 0.627-0.774; P=0.038), respectively. Conclusions: In children with UTIs, uNGAL levels may be associated with blood leukocyte differential counts. uNGAL measurements and monocyte counts can be helpful in children with suspected UTIs.

• Clinical and Experimental Pediatrics
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• v.61 no.1
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• pp.24-29
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• 2018

Purpose: The aim of this study was to evaluate the diagnostic accuracy of urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (uNGAL) and ${\beta}-2$ microglobulin (uB2MG), in early detection of urinary tract infection (UTI) in infants aged <3 months with fever. Methods: A total of 422 infants aged <3 months (male:female=267:155; mean age, 56.4 days), who were admitted for fever, were retrospectively included in this study. We compared uNGAL and uB2MG between the UTI and non-UTI groups at the time of admission. The sensitivity, specificity, accuracy, and area under the curve (AUC) of uNGAL and uB2MG for use in diagnosing UTI were assessed. Results: Among 422 patients, 102 (24.2%) were diagnosed with UTI. Levels of uNGAL were higher in the UTI group than in the non-UTI group (366.6 ng/mL vs. 26.9 ng/mL, P<0.001). Levels of uB2MG were not different between the 2 groups. Multivariate analysis revealed that uNGAL was an independent predictive factor for UTI (P=0.033). The sensitivity, specificity, and accuracy were 90.2%, 92.5%, and 91.9% for uNGAL, and 48.0%, 43.8%, and 44.8% for uB2MG, respectively. AUC of uNGAL was 0.942 and that of uB2MG was 0.407. Conclusion: Accuracy of uNGAL in the diagnosis of UTI is high in febrile infants aged <3 months. uNGAL can help in the early diagnosis and treatment of UTI in infants.

• Childhood Kidney Diseases
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• v.25 no.2
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• pp.84-91
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• 2021

Purpose: We aimed to study the association of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and leukocyte differential count in children with febrile urinary tract infection (UTI). Methods: Medical records of 154 children aged 1 month to 13 years with febrile UTI who were hospitalized were retrospectively reviewed. Associations between pNGAL levels and blood leukocyte differential count at admission and after 48 hours of treatment were investigated in children with or without acute pyelonephritis (APN). Results: The APN group (n=82) showed higher pNGAL levels, neutrophil count, monocyte count, and neutrophil-to-lymphocyte ratio (NLR), compared to the non-APN group (n=72) (all P<0.05). After adjustment for age and sex, pNGAL showed positive correlations with neutrophil count and NLR in both groups (all P<0.05). Additionally, it was correlated with the monocyte-to-lymphocyte ratio (MLR) only in the APN group (P<0.05). Before and after treatment, pNGAL was positively correlated with neutrophil count, NLR, and MLR in patients with APN while it was related with neutrophil count and NLR in those without APN (all P<0.05). Areas under the receiver operating curve of pNGAL, neutrophil count, NLR, and MLR for predicting APN were 0.804, 0.760, 0.730, and 0.636, respectively (all P<0.05). Only pNGAL was independently associated with the presence of APN in a multivariable logistic regression analysis (P<0.05). Conclusion: In children with febrile UTIs, pNGAL might be associated with leukocyte differential count and the presence of APN.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.2
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• pp.49-53
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• 2016

Acute kidney injury (AKI) is a common syndrome resulting in kidney damage and malfunction within a few days or even a few hours. The diagnosis of AKI depends on routine biochemical tests, including serum creatinine, aspartate aminotransferase (AST), alanine aminotransaminase (ALT), blood urea nitrogen (BUN), and electrolytes. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker that shows correlation with the severity of acute infections and kidney injuries. The predictive value in other conventional assays for kidney functions has been reported to cause distraction for AKI syndrome. The aim of this study is to verify the predictive value of plasma NGAL in patients with established AKI. The NGAL kit for checkup demonstrates sensitivity of ${\geq}300$ (92.2%), ${\geq}200$ (95.6%), ${\geq}100$ (99.6%), specificity of ${\geq}300$ (95.1%), ${\geq}200$ (97.3%), ${\geq}100$ (99.4%), positive predictability of ${\geq}300$ (93.3%), ${\geq}200$ (93.4%), ${\geq}100$ (99.2%), and negative predictability of ${\geq}300$ (96.7%), ${\geq}200$ (97.7%), ${\geq}100$ (98.1%), respectively. The plasma NGAL compared with the enzyme-linked immunosorbent assay (ELISA) has been shown to be an early predictive biomarker of AKI. The NGAL kit, recently developed for point-of-care of plasma specimens, is thought to be a useful and reliable biomarker for the early diagnosis of decreased kidney functions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6899-6904
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• 2014

NGAL (neutrophil gelatinase-associated lipocalin) is a novel cancer-related protein involves multiple functions in many cancers and other diseases. We previously overexpressed NGAL to analyze its role in esophageal squamous cell carcinoma (ESCC). In this study, a protein-protein interaction (PPI) was constructed and the shortest paths from NGAL to transcription factors in the network were analyzed. We found 28 shortest paths from NGAL to RELA, most of them obeying the principle of extracellular to cytoplasm, then nucleus. These shortest paths were also prioritized according to their normalized intensity from the microarray by the order of interaction cascades. A systems approach was developed in this study by linking differentially expressed genes with publicly available PPI data, Gene Ontology and subcellular localizaton for the integrated analyses. These shortest paths from NGAL to DEG transcription factors or other transcription factors in the PPI network provide important clues for future experimental identification of new pathways.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.105-110
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• 2019

Purpose: We sought to determine associations of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), known markers of renal injury, with hematuria in children and adolescents. Methods: A total of 112 urine samples from 72 patients aged 2 to 18 years with hematuria were enrolled in this study. Urinary concentrations of NGAL and L-FABP were measured by ELISA and compared between subjects with and without proteinuria and between subjects with and without glomerulonephritis diagnosed by renal biopsy. Results: Urinary concentrations of NGAL and L-FABP/creatinine (Cr) in subjects with proteinuria were not significantly different from those in subjects without proteinuria. They were not significant different between subjects with and without glomerulonephritis either. However, both concentrations of urinary NGAL and L-FABP/Cr were positively associated with urinary protein to creatinine ratio. Their levels had a tendency to be increased when proteinuria developed at later visits in subjects with hematuria only at initial visits. Conclusion: Monitoring urinary NGAL and L-FABP levels in addition to conventional risk factors such as proteinuria and serum creatinine might improve the prediction of renal injury in pediatric patients with hematuria.

• Neonatal Medicine
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• v.28 no.2
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• pp.65-71
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• 2021

Purpose: We investigated whether consecutive levels of new emerging renal biomarkers, including serum cystatin C (CysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL)/creatinine (Cr) ratio, were affected by postconceptional age in very-low-birth-weight (VLBW) infants. Methods: Repeatedly measured samples for each infant were divided into four groups according to postnatal age: at birth (stage I), 3 to 7 days postnatally (stage II), 8 to 28 days postnatally (stage III), and >28 days postnatally (stage IV). The association between renal biomarkers and postconceptional age was assessed using Pearson's correlation coefficient, and the mean values of renal biomarkers in the four stages were compared using repeated-measures analysis of variance. Results: For samples measured at birth, serum CysC (r=-0.358, P=0.032) and urinary NGAL/Cr ratio (r=-0.522, P=0.001) were negatively correlated with gestational age, whereas serum Cr (r=0.148, P=0.390) was not. In addition, for all samples measured, serum CysC (r=-0.209, P=0.012), urinary NGAL/Cr ratio (r=-0.536, P<0.001), and serum Cr (r=-0.311, P<0.001) were negatively correlated with postconceptional age. Compared with the mean values of the postnatal age-specific stages, serum CysC showed no significant differences in any of the four stages. However, the urinary NGAL/Cr ratio in stage IV was significantly different from those in stages I to III. Conclusion: Although urinary NGAL/Cr ratio and serum CysC were negatively correlated with postconceptional age considering renal development, serum CysC showed no significant differences in any of the four postnatal age-specific stages. Urinary NGAL/Cr ratio at >28 days postnatally seems to be more affected by postconceptional age than serum CysC in VLBW infants.