• Clinical and Experimental Pediatrics
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• 제61권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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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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• 제15권2호
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• pp.116-124
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• 2011

Acute kidney injury (AKI) can result in mortality or progress to chronic kidney disease in hospitalized patients. Although serum creatinine has long been used as the best biomarker for diagnosis of AKI, it has some clinical limitations, especially in children. New biomarkers are needed for early diagnosis, differential diagnosis, and reliable prediction of prognosis in AKI. Up to the present, candidate AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), livertype fatty acid-binding protein (L-FABP), matrix metalloproteinase-9 (MMP-9), and Nacetyl-$\ss$-D-glucosaminidase (NAG). However, whether these are superior to serum creatinine in the confirmation of diagnosis and prediction of prognosis in AKI is unclear. Further studies are needed for clinical application of these new biomarkers in AKI.

• Natural Product Sciences
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• 제28권4호
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• pp.194-200
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• 2022

Albizia julibrissin Durazz. (AJ; family Minosaceae) is widely distributed worldwide, and its stem bark has been used as a traditional herbal medicine. Acute kidney injury (AKI) is a clinical syndrome that results in sudden loss of renal function. This study aimed to investigate the effects of AJ against cisplatin-induced AKI using a human kidney proximal tubule epithelial cell line (HK-2) and cisplatin-treated mice. In vitro, cisplatin treatment increased apoptosis in HK-2 cells. However, AJ treatment decreased apoptosis of cisplatin-treated HK-2 cells. In vivo, cisplatin treatment accelerated renal injury by increasing the levels of renal injury markers, such as blood urea nitrogen, creatinine, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin, which were reversed by AJ treatment. Histopathologically, AJ treatment resulted in decreased renal damage with less tubular necrosis and brush border desquamation compared with the AKI group. Additionally, cisplatin treatment upregulated mitochondrial fission, a pathological characteristic of AKI, which was downregulated by AJ treatment. Along with increased mitochondrial fission, AJ treatment also reduced cisplatin-induced apoptosis. These results suggest that AJ may be a potential therapeutic agent for cisplatin-induced AKI.

• Neonatal Medicine
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• 제28권2호
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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.

• Childhood Kidney Diseases
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• 제20권2호
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• pp.63-68
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• 2016

Purpose: Disruption of normal renal development can lead to congenital anomalies of the kidney and urinary tract, including renal hypodysplasia. We aimed to clarify whether small kidney size affects clinical manifestations in children with urinary tract infection (UTI). Methods: One hundred fifty-four patients who had their first symptomatic UTI between January 2014 and June 2015 were enrolled in this study. Differences in kidney size were estimated based on percent uptake of $^{99m}Tc-$ dimercaptosuccinic acid (DMSA) in scintigraphy. The patients who showed more than 10% difference in kidney size on DMSA scintigraphy with none or minimal cortical defects were included in group A. (group A, n=17). Laboratory, clinical, and imaging results were compared with those of the other patients (group B, n=137). Results: Group A had a relatively higher incidence of vesicoureteral reflux than group B (44% vs 20%, P<0.05). The levels of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum C-reactive protein were significantly higher in group A (193 [64-337] vs 91 [59-211] ng/mL and 4.1 [0.5-11.9] vs 2.1 [0.7-5.3] ng/mL, respectively; all P <0.05). Linear regression analysis revealed that plasma NGAL level strongly correlated with the difference in renal uptake in DMSA scintigraphy in group A ($R^2=0.505$). Conclusion: The difference in kidney size could influence the clinical course and severity of pediatric UTI.

• Clinical and Experimental Pediatrics
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• 제63권4호
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• pp.151-156
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• 2020

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Toxicological Research
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• 제28권3호
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• 대한한의학방제학회지
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• 제29권1호
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• pp.33-44
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• 2021

Renal ischemia-reperfusion injury(IRI), an important cause of acute renal failure (ARF), cause increased renal tubular injury. Jesaeng-sinkihwan (JSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon (方藥合編)". JSH has been used for treatment of diabetes and glomerulonephritis with patients. Here we investigate the effects of Jesaeng-sinkihwan (JSH) in a mouse model of ischemic acute kidney injury. The animals model were divided into four groups at the age of 8 weeks; sham group: C57BL6 male mice (n=9), I/R group: C57BL6 male mice with I/R surgery (n=9), JSH Low group: C57BL6 male mice with surgery + JSH 100 mg/kg/day (n=9) and JSH High group: C57BL6 male mice with surgery + JSH 300 mg/kg/day (n=9). Ischemia was induced by clamping the both renal arteries during 25 min, and reperfusion was followed. Mouse were orally given with JSH (100 and 300 mg/kg/day during 3 days after surgery. Treatment with JSH significantly ameliorates creatinine clearance(Ccr), Creatinine (Cr) and blood urea nitrogen(BUN) in obtained plasma. . Treatment with JSH reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). JSH also reduced the periodic acid schiff (PAS) staining intensity and picro sirius red staining intensity in kidney of I/R group. These findings suggest that JSH ameliorates tubular injury including renal dysfunction in I/R induced ARF mouse.