INTRODUCTION: Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit. METHODS: This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m², and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test. RESULTS: A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE. CONCLUSION Serum NGAL identifies AKI and predicts three-month mortality.
Humans ; Lipocalin-2 ; Prospective Studies ; Lipocalins ; Proto-Oncogene Proteins ; Acute-Phase Proteins ; Biomarkers ; Acute Kidney Injury/diagnosis* ; Emergency Service, Hospital ; Predictive Value of Tests

Objective: To explore the performance of a self-made venous-venous bypass (VVB) device for liver transplantation based on the principle of magnetic levitation drive. Methods: Experimental study was conducted from August 2020 to January 2022. Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava. The animals were divided into two groups according to the VVB devices used during VVB. A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3). The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion, during vascular occlusion, 30 minutes, 60 minutes, 90 minutes after the start of VVB, and 30 minutes after vascular opening. In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared. The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures. Results: During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy, the peristalsis was normal, and the urine output was normal. There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were (71.0±7.7)mmHg(1 mmHg=0.133 kPa) and (74.0±8.7)mmHg,central venous pressure were (7.0±1.4)cmH₂O(1 cmH₂O=0.098 kPa) and (7.7±0.6)cmH₂O,heart rate were (131±10) beats/minutes and (132±8)beats/minutes; red blood cell count were (6.43±0.89)×10¹²/L and (6.32±0.58)×10¹²/L,hemoglobin were (108.4±5.9)g/L and (110.0±3.5)g/L,free hemoglobin were (78.28±3.96)mg/L and (78.08±4.54)mg/L; intestinal fatty acid binding protein were (2.27±0.49)μg/L and (2.40±0.78)μg/L;creatinine were (68.30±9.77)μmol/L and (79.90±26.91)μmol/L,blood urea nitrogen were (3.94±1.39)mmol/L and (3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were (4.02±0.53) μg/L and (3.86±0.23)μg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were (6.18±2.62)mmol/L and (4.30±0.50)mmol/L,concentrations of Na⁺ were (136.3±3.0)mmol/L and (137.6±1.6) mmol/L,concentrations of K⁺ were (3.89±0.42) mmol/L and (3.98±0.17)mmol/L,concentrations of Ca²⁺ were (1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05). Conclusion: The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.
Animals ; Creatinine ; Fatty Acid-Binding Proteins ; Gelatinases ; Lactic Acid ; Lipocalins ; Liver Transplantation ; Magnetic Phenomena ; Portal Vein/surgery* ; Swine ; Swine, Miniature

No abstract available.
Acute Kidney Injury* ; Lipocalins* ; Neutrophils* ; Plasma* ; Renal Insufficiency, Chronic*

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.
Adipokines ; Adipose Tissue, Brown ; Animals ; Caloric Restriction ; Diet, High-Fat ; Inflammation ; Lipocalins ; Macrophages ; Mice ; Mice, Obese ; Mitochondrial Dynamics ; Neutrophils ; Obesity ; Oxidative Stress ; Phenotype

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.
Adolescent ; Biopsy ; Child ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Glomerulonephritis ; Hematuria ; Humans ; Lipocalins ; Neutrophils ; Proteinuria ; Risk Factors

Human lipocalin 6 (hLCN6) is an epididymis-specific secretory protein. It binds to sperm and plays important role in sperm maturation. To explore the feasibility for isolating spermatozoa from mixed cells using anti-hLCN6 monoclonal antibody-conjugated immunomagnetic beads (anti-hLCN6 IMBs) and establish a new method for the separation of sperms from mixed stains, 2 sets of 30 cases of cell mixture suspensions and stains containing different proportions of sperm and epithelial cells were prepared. Biotin-labeled anti-hLCN6 monoclonal antibody (mAb) was incubated with the cell mixtures, and the spermatozoa were then isolated with avidin-coated IMBs. Sperm DNA was extracted and analyzed by PCR-STR typing. Differential lysis was also conducted to compare the effect of the two different isolation methods. The dissociation constant (Kd) of anti-hLCN6 mAb was 3.47×10⁻⁹ mol/L measured by ELISA. Western blotting and immunofluorescence assays showed that hLCN6 was detectable on sperm cells and mainly located on the post-acrosomal region of the sperm head, but not in epithelial cells. Anti-hLCN6 IMBs could capture and separate the sperm cells successfully. Microscopic observation showed that the IMBs could bind to the head of sperm specifically. The success rate of STR typing (more than 13 STR loci, RFU>200) was 90% when the number of sperm cells was 10³/mL and 100% when the sperm cells number was equal to or more than 10⁴/mL. When the number of sperm cells was 10³/mL, 10⁴/mL and 10⁵/mL in mixed stain samples, the success rate of STR typing were 40%, 90% and 100%, respectively. Taken together, the anti-hLCN6 immunomagnetic beads (IMB) method described here could be effective for the isolation of sperm from mixed cells, and the success rate was higher than that of the traditional differential lysis strategy. IMB sorting is a simple and efficient method for the separation of sperms from sperm and epithelial cell mixture, and can be utilized as a supplementary method for forensic mixture samples analysis in sexual assault cases.
Cell Separation ; DNA ; Humans ; Immunomagnetic Separation ; Lipocalins ; Male ; Polymerase Chain Reaction ; Spermatozoa

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC). METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups. RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI. CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.
Acute Kidney Injury ; Azotemia ; Creatinine ; Diagnosis ; Diagnosis, Differential ; Hand ; Hepatorenal Syndrome ; Hospital Mortality ; Humans ; Kidney Tubular Necrosis, Acute ; Lipocalins ; Liver Cirrhosis ; Liver Diseases ; Liver ; Necrosis ; Neutrophils ; Prospective Studies

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC).METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups.RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI.CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.
Acute Kidney Injury ; Azotemia ; Creatinine ; Diagnosis ; Diagnosis, Differential ; Hand ; Hepatorenal Syndrome ; Hospital Mortality ; Humans ; Kidney Tubular Necrosis, Acute ; Lipocalins ; Liver Cirrhosis ; Liver Diseases ; Liver ; Necrosis ; Neutrophils ; Prospective Studies

Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet. Recently, in vitro, in vivo, and clinical studies reported the association between LCN2 and the risk of Alzheimer's disease (AD). Here, we reviewed the significant evidences showing that LCN2 contributes to the onset and progression of AD. It may suggest that the manipulation of LCN2 in the CNS would be a crucial target for regulation of the pathogenesis and risk of AD.
Alzheimer Disease ; Astrocytes ; Biological Processes ; Bone Marrow ; Brain ; Cell Movement ; Cell Survival ; Central Nervous System ; Diagnosis ; Epithelial Cells ; Glycoproteins ; In Vitro Techniques ; Inflammation ; Insulin Resistance ; Kidney ; Lipocalins ; Liver ; Microglia ; Neurons ; Prognosis ; Uterus

BACKGROUND/AIMS: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. CONCLUSIONS: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.
Antiviral Agents* ; Biomarkers ; Cohort Studies ; Follow-Up Studies ; Gelatinases ; Glomerular Filtration Rate* ; Hepacivirus ; Hepatitis ; Hepatitis C, Chronic ; Humans ; Inflammation ; Kidney ; Lipocalins* ; Neutrophils* ; Reference Values ; Retrospective Studies