Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Hepcidin and Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Acute Kidney Injury Linked Iron Metabolism

No abstract available.

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

BACKGROUND: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. METHODS: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. RESULTS: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. CONCLUSIONS: NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.

Clinical Significance of the Interval Change of Plasma Neutrophil Gelatinase-Associated Lipocalin in Acute Kidney Injury and Acute Kidney Injury Superimposed on Chronic Kidney Disease / 전남의대학술지

No abstract available.

Separation and forensic identification of sperm from cell mixtures using anti-hLCN6 monoclonal antibody coupled magnetic beads / 生物工程学报

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.

The associations of Urinary Neutrophil Gelatinaseassociated Lipocalin (NGAL) and Liver-type Fatty Acidbinding Protein (L-FABP) Levels with Hematuria in Children and Adolescents

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.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기학회지

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.

Effects of caloric restriction on the expression of lipocalin-2 and its receptor in the brown adipose tissue of high-fat diet-fed mice

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.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기병학회잡지

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.

Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals

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.

Perspectives in Lipocalin-2: Emerging Biomarker for Medical Diagnosis and Prognosis for Alzheimer's Disease

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.

Plasma Neutrophil Gelatinase-Associated Lipocalin as a Marker of Tubular Damage in Diabetic Nephropathy

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±5.3 ng/mL, 93.4±71.8 ng/mL, and 1,536.9±554.9 ng/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.

Neutrophil Gelatinase-Associated Lipocalin as a Promising Novel Biomarker for Early Detection of Kidney Injury

No abstract available.

Plasma Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Renal Parenchymal Involvement in Infants With Febrile Urinary Tract Infection: A Preliminary Study

BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in infants. Renal parenchymal involvement is an important prognostic factor; however, early detection of parenchymal involvement in UTI may be difficult during infancy. This study aimed to assess whether a recently established biomarker of UTI, neutrophil gelatinase-associated lipocalin (NGAL), can serve as a useful marker for the detection of cortical defects (CD) and to determine the appropriate diagnostic cut-off value of NGAL in infants with febrile UTI. METHODS: Infants hospitalized for febrile UTI were divided into two groups according to the presence of cortical defects on dimercaptosuccinic acid (DMSA) scintigraphy. Among 64 enrolled infants, 43 (67%) had CD (UTI-CD) and 21 (33%) had no CD (UTI-ND). The white blood cell count, C-reactive protein, and plasma NGAL (pNGAL) levels were determined before antibiotic therapy and compared between the two groups. RESULTS: pNGAL level was significantly higher in the UTI-CD group than in the UTI-ND group (340 µg/L vs 214 µg/L, P=0.002). Multivariate analysis showed that pNGAL level was the only independent predictor of CD (odds ratio 2.759, P=0.039). In the ROC curve analysis, pNGAL showed the highest area under the curve (0.745; 95% confidence interval, 0.561–0.821; P=0.014). The appropriate cut-off value of pNGAL was 267 µg/L (sensitivity, 72.1%; specificity, 71.4%). CONCLUSIONS: pNGAL was found to be a useful marker for early prediction of renal parenchymal involvement in infants with febrile UTI.

Neutrophil Gelatinase-associated Lipocalin as a Predictor of Acute Kidney Injury in Patients during Treatment with Colistimethate Sodium

BACKGROUND: The emergence of multidrug-resistant, Gram-negative bacteria has resulted in reconsideration of colistimethate sodium (CMS) as a last resort for treatment of such infections. However, acute kidney injury (AKI) may represent a major limiting adverse effect of use of CMS. Early AKI detection in CMS-treated patients can help prevent progression to acute failure and reduce the need of renal replacement therapy. We hypothesized that plasma neutrophil gelatinase-associated lipocalin (NGAL) may be an early biomarker of AKI in CMS-treated patients. MATERIALS AND METHODS: This prospective cohort study included patients aged ≥20 years who received intravenous CMS between March 2014 and November 2015. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria. The primary endpoint was the difference between the average time to AKI onset based on serum creatinine and empirically derived plasma NGAL levels. RESULTS: Among 109 CMS-treated patients, 23 patients (mean age, 61.3 ± 16.1 years; men, 65.2%) were evaluated. Thirteen (56.5%) patients fulfilled the AKI criteria. The mean time to AKI onset based on serum creatinine after CMS initiation was 78.15 ± 30.49 hours. AKI was detected approximately 22 hours earlier using plasma NGAL than when using serum creatinine as an indicator of AKI (P = 0.035). The baseline plasma NGAL level was 264.0 ± 167.3 ng/mL and 192.7 ± 65.3 ng/mL in patients with and without AKI, respectively (P = 0.218). The area under the curve for plasma NGAL level at 56 hours was 0.796 (95% confidence interval, 0.609–0.983; P = 0.017), with a sensitivity and specificity of 69.2% and 90.0%, respectively (cutoff value, 285 ng/mL). CONCLUSION: NGAL level was found to be a strong predictor of AKI. This study provides additional evidence of the utility of NGAL for AKI in patients with treated CMS. Plasma NGAL represent sensitive and specific predictive early biomarkers for AKI in patient treated CMS.

Neutrophil Gelatinase-associated Lipocalin as a Predictor of Acute Kidney Injury in Patients during Treatment with Colistimethate Sodium

BACKGROUND: The emergence of multidrug-resistant, Gram-negative bacteria has resulted in reconsideration of colistimethate sodium (CMS) as a last resort for treatment of such infections. However, acute kidney injury (AKI) may represent a major limiting adverse effect of use of CMS. Early AKI detection in CMS-treated patients can help prevent progression to acute failure and reduce the need of renal replacement therapy. We hypothesized that plasma neutrophil gelatinase-associated lipocalin (NGAL) may be an early biomarker of AKI in CMS-treated patients. MATERIALS AND METHODS: This prospective cohort study included patients aged ≥20 years who received intravenous CMS between March 2014 and November 2015. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria. The primary endpoint was the difference between the average time to AKI onset based on serum creatinine and empirically derived plasma NGAL levels. RESULTS: Among 109 CMS-treated patients, 23 patients (mean age, 61.3 ± 16.1 years; men, 65.2%) were evaluated. Thirteen (56.5%) patients fulfilled the AKI criteria. The mean time to AKI onset based on serum creatinine after CMS initiation was 78.15 ± 30.49 hours. AKI was detected approximately 22 hours earlier using plasma NGAL than when using serum creatinine as an indicator of AKI (P = 0.035). The baseline plasma NGAL level was 264.0 ± 167.3 ng/mL and 192.7 ± 65.3 ng/mL in patients with and without AKI, respectively (P = 0.218). The area under the curve for plasma NGAL level at 56 hours was 0.796 (95% confidence interval, 0.609–0.983; P = 0.017), with a sensitivity and specificity of 69.2% and 90.0%, respectively (cutoff value, 285 ng/mL). CONCLUSION: NGAL level was found to be a strong predictor of AKI. This study provides additional evidence of the utility of NGAL for AKI in patients with treated CMS. Plasma NGAL represent sensitive and specific predictive early biomarkers for AKI in patient treated CMS.

Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection / 소아과

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (uNGAL) and β-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.

Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide-induced reactive oxygen species and mitogen-activated protein kinase expression in human renal proximal tubule epithelial cells

Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-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 µg/ml) in the presence or absence of a type 1 TACE inhibitor (1 µM) or type 2 TACE inhibitor (10 µM). LPS treatment induced increased serum creatinine, TNFα, 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.

Clinical significance of serum neutrophil gelatinase-associated lipocalin in the early diagnosis of renal function deterioration after radical nephrectomy / 고신대학교의과대학학술지

OBJECTIVES: The standard metrics used to monitor the progression of acute kidney injury (AKI) include markers such as serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate (eGFR). Moreover, neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported to modulate oxidative stress. METHODS: We aimed to evaluate the usefulness of serum NGAL levels for monitoring renal function after radical nephrectomy (RN). We prospectively collected data from 30 patients who underwent RN. We analyzed serum NGAL and creatinine at 6 time points: preoperative day 1, right after surgery, 6 hours after surgery, postoperative day (POD) 1, POD 3, and POD 5. We compared these measurements according to the eGFR values (classified as chronic kidney disease stage III; CKD III or not) using data obtained 3 months after surgery. RESULTS: The mean age was 65.5 years (range, 45–77 years), and the male-to-female ratio was 2:1. At the last follow-up examination, there were 12 patients (40%) with CKD III. Using receiver operating characteristic analysis, we found that serum creatinine on POD 5 (area under the curve [AUC], 0.887; P= 0.000) and NGAL at 6 hours after LRN (AUC, 0.743, P= 0.026) were significant predictors of CKD III. The development of CKD III after LRN was associated with the serum creatinine level on POD 5 and the NGAL at 6 hours after surgery. CONCLUSIONS: Compared to serum creatinine, serum NGAL enabled earlier prediction of postoperative CKD III. Therefore, serum NGAL measured 6 hours after surgery could be a useful marker for managing patients after RN.

Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus patients / Análise da expressão do gene da proteína beta-traço na urina de pacientes com diabetes mellitus tipo 2

ABSTRACT Objective: To evaluate the gene expression of beta-trace protein in urine of diabetic patients, with no reduction in glomerular filtration rate, which was defined as below 60mL/min/1.73m2. Methods: Type 2 diabetes mellitus patients were recruited, and a group of non-diabetic individuals served as control. Beta-trace protein gene expression was analyzed by quantitative PCR. Blood samples were collected to establish glucose levels and baseline kidney function. Accuracy was analyzed using ROC curves. Results: Ninety type 2 diabetes mellitus patients and 20 non-diabetic individuals were recruited. The area under the curve was 0.601, sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18% showed an expression above the cutoff point. Conclusion: These results of accuracy of beta-trace protein gene expression in urine of diabetic patients are promising, although they did not achieve a higher area under the curve level.

RESUMO Objetivo: Avaliar a expressão do gene da proteína beta-traço na urina de pacientes diabéticos, sem redução na taxa de filtração glomerular, definida como abaixo de 60mL/min/1,73m2. Métodos: Foram recrutados pacientes com diabetes mellitus tipo 2, e um grupo de indivíduos não diabéticos serviu como controle. A expressão do gene da proteína beta-traço foi analisada por PCR quantitativa. Amostras de sangue foram coletadas para estabelecer níveis de glicemia e função renal inicial. A acurácia foi analisada utilizando curvas ROC. Resultados: Foram recrutados 90 pacientes com diabetes mellitus tipo 2 e 20 não diabéticos. A área sob a curva foi de 0,601, com sensibilidade de 20% e especificidade de 89,47%. Entre os diabéticos, 18% apresentaram expressão acima do ponto de corte. Conclusão: Estes resultados de acurácia da expressão do gene da proteína beta-traço na urina de pacientes diabéticos são promissores, apesar de não terem atingido um nível alto na área sob a curva.