Neutrophil Gelatinase-associated Lipocalin Concentrations Research Articles

Measurement of Neutrophil Gelatinase-Associated Lipocalin Concentration in Canine Cerebrospinal Fluid and Serum and Its Involvement in Neuroinflammation.

Neutrophil gelatinase-associated Lipocalin (NGAL) is a glycoprotein involved in inflammation acting as an acute phase protein and chemokine as well as a regulator of iron homeostasis. NGAL has been shown to be upregulated in experimental autoimmune encephalomyelitis (EAE) in mice. Increased NGAL concentration in cerebrospinal fluid (CSF) and expression in central nervous system (CNS) has been described in human neuroinflammatory disease such as multiple sclerosis and neuropsychiatric lupus as well as in bacterial meningitis. We aimed to investigate involvement of NGAL in spontaneous canine neuroinflammation as a potential large animal model for immune- mediated neurological disorders. A commercially available Enzyme-linked Immunosorbent Assay (ELISA) for detection of canine NGAL was validated for use in canine CSF. Concentration in CSF and serum of canine patients suffering from steroid- responsive meningitis- arteriitis (SRMA), Meningoencephalitis of unknown origin (MUO), different non- inflammatory CNS disease and control dogs were compared. Relationship between NGAL concentration in CSF and serum and inflammatory parameters in CSF and blood (IgA concentration, total nucleated cell count (TNCC), protein content) as well as association with erythrocytes in CSF, duration of illness, plasma creatinine and urinary leucocytes were evaluated. In dogs with SRMA and MUO, CSF concentration of NGAL was significantly higher than in dogs with idiopathic epilepsy, compressive myelopathy, intracranial neoplasia and SRMA in remission (p < 0.0001). Patients with acute SRMA had significantly higher levels of NGAL in CSF than neurologically normal controls (p < 0.0001). Serum NGAL concentrations were significantly higher in dogs with SRMA than in patients with myelopathy and intracranial neoplasia (p < 0.0001). NGAL levels in CSF were strongly positively associated with IgA concentration (rSpear= 0.60116, p < 0.0001), TNCC (rSpear= 0.65746, p < 0.0001) and protein content (rSpear= 0.73353, p < 0.0001) in CSF. It can be measured in CSF of healthy and diseased dogs. Higher concentrations in canine patients with SRMA as well as positive association with TNCC in CSF suggest an involvement in pro-inflammatory pathways and chemotaxis in SRMA. High serum levels of NGAL in serum of SRMA patients in different stages of disease might reflect the systemic character of the disease.

Screening of Early Diagnostic Markers of Gentamicin-induced Acute Kidney Injury in Canines.

IntroductionThe value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs.Material and MethodsSubcutaneous gentamicin injection in 16 healthy adult beagles made the AKI model. Blood was sampled every 6 h to detect NGAL, Kim-1, L-FABP, and serum creatinine (SCr) concentrations. Kidney tissue of two dogs was taken before the injection, as soon as SCr was elevated (78 μmol/L), and when it had risen to 1.5 times the baseline, and haematoxylin-eosin staining and transmission electron microscopy (TEM) were used to observe changes.ResultsNGAL, Kim-1, and SCr levels were significantly increased (P < 0.05) at 18, 30, and 78 h post injection, but L-FABP concentration was not associated with renal injury. At the earliest SCr elevation stage, findings were mild oedema, degeneration, and vacuolisation in renal tubular epithelial cells in pathology, and mild cytoplasmic and mitochondrial oedema in TEM. At this time point, NGAL and Kim-1 concentrations were significantly increased (P < 0.05), indicating that these two molecules biomark early kidney injury in dogs. Using receiver operating characteristic curve analysis, their warning levels were > 25.31 ng/mL and > 48.52 pg/mL.ConclusionPlasma NGAL and Kim-1 above warning levels are early indicators of gentamicin-induced AKI in dogs.

Predictive performance of plasma neutrophil gelatinase-associated lipocalin for neurologic outcomes in out-of-hospital cardiac arrest patients treated with targeted temperature management: A prospective observational study.

Few studies have demonstrated the prognostic potential of neutrophil gelatinase-associated lipocalin (NGAL) in post-cardiac arrest patients. This study evaluated the usefulness of plasma NGAL in predicting neurologic outcome and mortality in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). A prospective observational study was conducted between October 2013 and April 2016 at a single tertiary hospital. We enrolled 75 patients treated with TTM and collected their demographic data, cardiopulmonary resuscitation-related information, data on plasma NGAL concentration, and prognostic test results. Plasma NGAL was measured at 4 hours after return of spontaneous circulation (ROSC). The primary endpoint was the neurologic outcome at discharge and the secondary outcome was 28-day mortality. Neurologic outcomes were analyzed using a stepwise multivariate logistic regression while 28-day mortality was analyzed using a stepwise Cox regression. The predictive performance of plasma NGAL for neurologic outcome was measured by the area under the receiver operating characteristic curve and the predictability of 28-day mortality was measured using Harrell C-index. We also compared the predictive performance of plasma NGAL to that of other traditional prognostic modalities for outcome variables. Thirty patients (40%) had good neurologic outcomes and 53 (70.7%) survived for more than 28 days. Plasma NGAL in patients with good neurologic outcomes was 122.7 ± 146.7 ng/ml, which was significantly lower than that in the poor neurologic outcome group (307.5 ± 269.6 ng/ml; P < .001). The probability of a poor neurologic outcome was more than 3.3-fold in the NGAL >124.3 ng/ml group (odds ratio, 3.321; 95% confidence interval [CI], 1.265–8.721]). Plasma NGAL in the survived group was significantly lower than that in the non-survived group (172.7 ± 191.6 vs 379.9 ± 297.8 ng/ml; P = .005). Plasma NGAL was significantly correlated with 28-day mortality (hazard ratio 1.003, 95% CI 1.001–1.004; P < .001). The predictive performance of plasma NGAL was not inferior to that of other prognostic modalities except electroencephalography. Plasma NGAL is valuable for predicting the neurologic outcome and 28-day mortality of patients with OHCA at an early stage after ROSC.This study was registered at ClinicalTrials.gov on November 19, 2013 (Identifier: NCT01987466).

Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENTWhat is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role.What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL’s ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary.

Urinary neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury in sepsis patients in the emergency department

BackgroundPlasma neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for predicting acute kidney injury (AKI). The purpose of this study was to evaluate the diagnostic performance of urinary NGAL in predicting AKI in sepsis patients in the emergency department. MethodsA total of 140 patients were enrolled. We compared serum procalcitonin and urinary NGAL concentrations between patients with local infection, sepsis, and septic shock, and between patients who did and did not develop AKI with sepsis. Receiver-operating characteristic curve analysis was used to evaluate the ability to predict AKI in sepsis patients. ResultsBoth serum procalcitonin and urinary NGAL concentrations were significantly higher in the sepsis and septic shock groups than in the local infection group (both p < 0.001). In sepsis patients, serum procalcitonin and urinary NGAL concentrations were higher in AKI patients than in those without AKI (p = 0.006, p < 0.001, respectively). The area under the curve for predicting of AKI was higher for a urinary NGAL of 0.820 (95% confidence interval (CI) 0.721–0.895) than for a serum procalcitonin concentration of 0.76 (95% CI 0.597–0.800). ConclusionUrinary NGAL concentration may predict AKI in patients with sepsis in the emergency department.

Circulating C1q/TNF-Related Protein 3, Omentin-1 and NGAL in Obese Patients with Type 2 Diabetes During Insulin Therapy.

The aim of the study was to quantify the plasma concentration of omentin-1, neutrophil gelatinase-associated lipocalin (NGAL), and complement C1q tumor necrosis factor-related protein-3 (CTRP3) in obese patients with type 2 diabetes, before introducing insulin therapy, in relation to the plasma expression profiles of these regulatory molecules in the same patients after a 6-month insulin mixture therapy and in obese controls. Elevated plasma NGAL concentrations were found in type 2 diabetic patients as compared with subjects with metabolically healthy obesity. In turn, a 6-month insulin mixture therapy has shown a marked increase in the plasma concentration of omentine-1 and a significant decrease in plasma CTRP3 concentration in obese patients with type 2 diabetes, in relation to the values found in these patients before the implementation of insulin therapy. Insulin mixture therapy has also proved to be an important factor modifying the plasma profile of NGAL, increasing the concentration of this bioactive molecule in the plasma of patients with type 2 diabetes, after 6 months of its use, in relation to the concentration before treatment. The significant changes in the plasma profile of omentin-1, NGAL and CTRP3 during insulin therapy suggest their potential diagnostic utility in monitoring metabolic changes associated with the introduction of insulin treatment in type 2 diabetic patients.

Urinary neutrophil gelatinase-associated lipocalin is associated with preeclampsia in a cohort of Turkish women

ABSTRACTPurpose: We investigated the optimal cut-off level for urinary neutrophil gelatinase-associated lipocalin (NGAL) in preeclamptic patients to confirm the diagnosis.Methods: Urinary NGAL concentrations were measured by specific enzyme-linked immunosorbent assay (ELISA).Results: Patients with preeclampsia had significantly higher urinary NGAL concentrations than controls (mean: 387 ng/ml vs. 188 ng/ml, respectively; P< 0.001). Using a cutoff value 252 ng/ml for urinary NGAL to confirm diagnosis of preeclampsia, sensitivity, and specificity were 92% and 91%, respectively.Conclusion: Urinary NGAL concentrations were significantly elevated in women with preeclampsia versus normotensive controls.

The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery

BackgroundAcute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery.MethodsTwo separate patient cohorts were studied: 1) the “kinetic cohort” (n = 29) and 2) the “FINNAKI cohort” (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the “FINNAKI cohort” Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson’s and Spearman’s tests were used as appropriate.ResultsThere was strong intraoperative association between NGAL and lactoferrin at all four time-points in the “kinetic cohort”. In the “FINNAKI cohort”, NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p < 0.001) and at admission to the intensive care unit (R = 0.69, p < 0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p < 0.001; lactoferrin: p < 0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3–53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0–64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 – 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients.ConclusionsPlasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.

Predictive value of plasma neutrophil gelatinase-associated lipocalin in acute charcoal-burning carbon monoxide poisoning.

This study aimed to assess the feasibility of using the plasma neutrophil gelatinase-associated lipocalin (NGAL) level at the time of presentation in the emergency department (ED) to predict acute kidney injury (AKI) and the long-term neurological outcomes of acute charcoal-burning carbon monoxide (CO) poisoning. This retrospective study included 260 patients who suffered acute charcoal-burning CO poisoning. The median plasma NGAL concentration at the time of presentation in the ED after acute charcoal-burning CO poisoning was 78 (54-115) ng/ml. The NGAL level was an independent predictor of AKI development and could be used to stratify the severity of AKI. However, the area under the receiver operating characteristic curve (AUC) of the predictive model for AKI that included both the plasma NGAL level and clinical parameters was comparable to that of the predictive model including only the clinical parameters. The plasma NGAL level at the time of presentation in the ED was an independent factor predicting long-term neurological outcomes in patients who did not develop AKI. In these patients, the plasma NGAL level significantly improved the predictive accuracy of the model when used in combination with clinical parameters. In contrast, the plasma NGAL level was not associated with long-term neurological outcomes in patients who developed AKI. Measurement of the plasma NGAL level at the time ED presentation might improve the prediction of long-term neurological outcomes in patients who do not develop AKI after acute charcoal-burning CO poisoning. However, it might not offer additional benefit for AKI prediction compared to previously used markers.

The clinical significance of neutrophil gelatinase‐associated lipocalin in ischemic stroke patients with acute kidney injury

BackgroundAcute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on the clinical outcomes. Neutrophil gelatinase‐associated lipocalin (NGAL), an acute phase protein, has been identified as a novel biomarker for acute kidney impairment. Here, we studied the early expression of NGAL in AIS patients with AKI and its clinic value in predicting and diagnosis of AKI after stroke.MethodsA total of 205 subjects diagnosed as first‐ever AIS were recruited in this study, including 40 AIS with AKI and 165 AIS without AKI defined using the KDIGO guidelines. The serum and urine levels of NGAL were measured with ELISA. To evaluate the clinic value of NGAL, we also detected creatinine, urea nitrogen and cystatin C and microalbumin (mALB) in serum or urine using chemiluminescence or immunoturbidimetry method, and then the receiver operating characteristic (ROC) curve and correlation was analyzed. The severity of AIS patients was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score.ResultsThe serum and urine NGAL levels were significantly increased in AIS patients with AKI, and line regression analysis indicated that there was a positive correlation between the serum NGAL and creatinine level in AIS patients accompanied AKI. Additionally, the concentration of serum NGAL in AIS patients with AKI increased with the severity of stroke.ConclusionThe increased serum NGAL may be used as a valuable complementary marker for the diagnoses and prediction of AKI in the early stage of AIS patients.

Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury

Metabolic acidosis occurs due to insufficient urinary ammonium excretion as chronic kidney disease (CKD) advances. Because obese subjects tend to have excessive consumption of protein and sodium chloride, they are prone to chronic acid loading and may therefore be predisposed to acid-induced kidney injury. We investigated the involvement of obesity in ammoniagenesis within damaged kidneys. In the clinical study, urinary ammonium excretion was compared between 13 normal-weight and 15 overweight/obese CKD outpatients whose creatinine clearance was higher than 25 mL/min. For animal experiments, NH4 Cl was loaded to KKAy/TaJcl (KKAy), a metabolic syndrome model, and control BALB/c mice for 20 weeks. Kidney injury was evaluated through histological analysis and the expression of proinflammatory markers. Urinary ammonium excretion was lower in overweight/obese patients than in normal-weight patients, while intakes of protein and sodium chloride were higher in overweight/obese patients, implying that subclinical metabolic acidosis occurs in overweight/obese patients. The increase in urinary ammonium excretion induced by NH4 Cl loading was attenuated in KKAy mice after 16 weeks, whereas the increase was maintained in BALB/c mice throughout the study period. Histological study and real-time polymerase chain reaction analysis showed proximal tubular injury and enhanced expression levels of neutrophil gelatinase-associated lipocalin (NGAL) protein and messenger RNA, respectively, in KKAy mice but not in BALB/c mice. Finally, urinary NGAL concentration was higher in overweight/obese patients than in normal-weight patients in the early stage of CKD. Obesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.

Development of a novel immunoassay for the simple and fast quantitation of neutrophil gelatinase-associated lipocalin using europium(III) chelate microparticles and magnetic beads

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for diagnosing acute kidney injury (AKI). Currently, there are few assays for determining NGAL and they are complex, time-consuming or expensive. We aimed to establish an efficient immunoassay to measure NGAL in human urine simply and rapidly. A novel immunoassay for NGAL determination was established by combining a dissociation-enhanced-free time-resolved fluoroimmunoassay (TRFIA) and immunomagnetic separation. Based on a “sandwich”-type immunoassay format, analytes in samples were captured by a pair of monoclonal antibodies (mAb) in which one mAb was coated in magnetic beads and the other mAb was labeled with europium(III) chelate microparticles (CM-EUs) as “fluorescent reporters”. NGAL concentrations were determined in a linear range (10–1500 ng mL−1) with a limit of detection of 0.32 ng mL−1. The reproducibility, recovery, and specificity of our TRFIA were acceptable. Our method was compared with that of a chemiluminescence immunoassay (CMIA) using 115 urine samples, and the results showed good correlation (R2 = 0.8677). We expect our novel method to be useful for the early diagnosis of AKI.

The Effect of Serum Neutrophil Gelatinase-Associated Lipocalin on the Discontinuation of Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury

Background: To determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating serum neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with acute kidney injury (AKI). Methods: A prospective observational study was conducted from September 2015 to March 2018. AKI patients treated with CRRT for at least 24 h were divided into “success” and “failure” groups according to their RRT requirement within 7 days after the initial discontinuation of CRRT. The prefilter and effluent NGAL concentrations were measured to calculate the sieving coefficient (SC) of NGAL in all included subjects from 0 to 72 h. Results: In total, 110 patients were divided into success (n = 78) and failure groups (n = 32). The mean SC of NGAL during CRRT was less than 0.05. The patients in the failure group were associated with higher mortality compared with patients in the success group (37.5 vs. 12.8%, respectively, p = 0.013). There were significant differences in serum NGAL, creatinine, and urine output at discontinuation. In patients without sepsis (n = 70), serum NGAL and urine output were significant predictors of successful cessation. The area under the receiver operating characteristic to predict the successful discontinuation of CRRT was 0.88 for NGAL and 0.86 for urine output. An NGAL level of 403 ng/mL had the highest sensitivity (81%) and specificity (89%) and a urine output of 695 mL/day had the highest sensitivity (83%) and specificity (88%). However, in septic patients (n = 40), urine output but not serum NGAL (OR 0.999, p = 0.69) was a significant variable (OR 1.002, p = 0.005), with a cutoff of 796 mL/day (sensitivity 83%, specificity 88%). Conclusions: Serum NGAL was a significant factor for predicting successful CRRT discontinuation in nonseptic AKI patients. However, urine output, rather than serum NGAL, was a significant predictor in septic AKI patients.

Urinary acute kidney injury biomarkers in very low-birth-weight infants on indomethacin for patent ductus arteriosus.

Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration. Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatalmodified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophilgelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered. While urinary [TIMP-2]•[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.

Urine KIM-1 as a Potential Biomarker of Acute Renal Injury After Circulatory Collapse in Children.

Serum creatinine (SCr) is a late marker of acute kidney injury (AKI) due to the lag time between initiating injury and loss of function. We assessed the ability of urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) to predict AKI in critically ill children with circulatory collapse. Serum creatinine, estimated creatinine clearance (eCrCL), urine IL-18, KIM-1, and NGAL values were measured in 86 children with circulatory collapse on the day of admission, and the results were compared with those obtained 6 days later. Acute kidney injury was defined as a decrease in eCrCL of greater than 25% within the first 48 hours of enrollment. Areas under the curve (AUC) for receiver operating characteristic curve were calculated for the early detection of AKI. Mean SCr concentration did not differ significantly during the first 6 days of hospital admission. In contrast, mean urine concentrations of IL-18, KIM-1, and NGAL rose significantly from day of admission to the sixth day of hospital stay (P < 0.001). Urinary KIM-1 emerged as having the strongest performance for the early detection of AKI, followed by NGAL, IL-18, and eCrCL. Urinary KIM-1 displayed the highest AUC of 0.81 (95% confidence interval [CI], 0.76-0.93; P < 0.001) for the early detection of AKI after circulatory collapse, followed by NGAL (0.77% CI, 0.70-0.84) and IL-18 (0.69% CI, 0.48-0.64). Of a panel of 3 promising urinary biomarkers, KIM-1 demonstrated the best performance in predicting AKI in children with circulatory collapse before a change in SCr or eCrCL becomes apparent.

The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms

In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. In this observational study, aneurysm tissue and blood of ruptured (n=13) AAA patients were investigated versus nonruptured (n=26) patients. Nondilated aortas (n=5) from deceased patients and venous blood from healthy volunteers (n=10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. NGAL (in μg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P<0.01) and 14 (range 12-22) in controls (P<0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P=0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs=0.80, P<0.01), MMP-9 (Rs=0.56, P=0.02), and caspase-3 (Rs=0.75, P=0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P=0.34 and P=0.95, respectively). This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.

Association between urodynamic parameters and urine neutrophil gelatinase–associated lipocalin concentrations in children with neuropathic bladders

Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury, and has been shown to be a sensitive marker of renal damage in urinary tract obstruction. Children with neurogenic bladders are at risk of renal damage as a result of increased pressure within the urinary system. A marker of upper tract deterioration in this population would be useful to guide management. The aim of the study is to compare urinary NGAL (uNGAL) concentrations between children who have elevated and normal detrusor pressureand between those with low and normal compliance, on urodynamics. This is a cross-sectional study of children with neurogenic bladder who underwent routine urodynamics from August2015 to March2016. Patients with positive urine cultures from the time of urodynamics were excluded from analysis. Urine was obtained from the time of urodynamics for uNGAL measurement. Urodynamics were reviewed. High pressure is defined as a detrusor pressure of 40cm of water or greater at the volume where catheterization is normally performed. Compliance was calculated at the volume where catheterization is performed. A total of 89 patients were included (low pressure, n=73; high pressure, n=16 and low compliance, n=41; normal compliance, n=40). Median uNGAL concentrations were not different between patients with low and high pressure, but there was a higher median uNGAL concentration in patients with normal compliance compared with those with low compliance. There was no correlation between maximum detrusor pressure and uNGAL concentration, but there was a moderate relationship between compliance and uNGAL concentration (rs=0.43, p<0.01 for non-normalized uNGAL and rs=0.30, p<0.01 for normalized uNGAL). There is an increase in uNGAL concentrations in patients with normal compliance compared with those with low compliance, but no difference between patients with low or high pressure.

Relationship between neutrophil gelatinase-associated lipocalin, cardiac biomarkers, inflammation index and renal parameters in cardiovascular disease

The plasma neutrophil gelatinase-associated lipocalin (NGAL) level is elevated in myocardial infarction (MI) and affected by inflammation and kidney function. The aim of this study was to determine which of these conditions more critically affects the plasma NGAL level in MI. Patients with MI were evaluated by measuring the NGAL concentration and its corrected values. No significant association was observed between plasma NGAL concentration and cardiac biomarkers. However, the NGAL/inflammation index ratio (NGAL/Inf ratio) was positively correlated with troponin-I (r=0.289, p&lt;0.001), and the NGAL/serum creatinine ratio (NGAL/sCr ratio) was significantly correlated with creatine kinase-MB (r=0.251, p&lt;0.001). After adjusting for inflammation and kidney function, increased NGAL concentrations returned to baseline levels, which were not different from those of healthy individuals. The percent difference between NGAL and the NGAL/Inf ratio was 35.6%, significantly higher than that between NGAL and the NGAL/sCr ratio (15.4%; p&lt;0.001). The severity of inflammation seems to play a more crucial role than renal and myocardial dysfunction in affecting plasma NGAL levels in MI. Plasma NGAL levels need to be corrected using the inflammation index and sCr levels for exactly evaluating patients with MI.

Renoprotective effect of oral rehydration solution III in exertional heatstroke rats

Aim: Exertional heastroke (EHS) can lead to acute kidney injury. Oral rehydration solution III (ORS III), recommended by WHO in 2004, is used to rehydrate children with gastroenteritis. This study aimed to characterize the renoprotective effect of ORS III in EHS rats.Methods: Rats were randomly divided into Group Control, Group EHS, Group EHS + Water, and Group EHS + ORS. Thirty minutes before the experiment, ORS III was orally administrated to Group EHS + ORS, Water was given to Group EHS + Water. Rats from Group EHS, Group EHS + Water and Group EHS + ORS were then forced to run until they fatigued. Core temperature (Tc) was monitored and 40.5 °C was considered as the onset of heatstroke. Serum creatinine (SCr), blood urea nitrogen (BUN) were measured using an automated biochemical analyzer. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured using an NGAL ELISA Kit. Light microscopy was used for kidney structural analysis.Results: SCr level in Group EHS was no different from Group Control (p > .05), while BUN and NGAL levels in Group EHS were higher than Group Control (p <.001, p < .001). SCr, BUN and NGAL concentrations in group EHS + Water were no different from Group EHS (p > .05). SCr, BUN levels in Group EHS + ORS were no different from Group EHS (p > .05). But NGAL levels were significant in these two groups (p = .012). Renal histopathologies of rats in Group EHS and Group EHS + Water showed flattened lumens filled with eosinophilic materials. The damage was milder in Group EHS + ORS, in which injured tubules showed degeneration of the tubular epithelium and sloughing of the brush border membrane.Conclusion: ORS III could alleviate the kidney injury in EHS rats.

Serum Neutrophil Gelatinase-associated Lipocalin Measured at Admission to Predict Mortality in Sepsis-associated Acute Kidney Injury of Vietnamese Critically Ill Patients

Purpose: To evaluate incidence of sepsis-associated acute kidney injury (SA-AKI) in the AKI Intensive Care Unit (ICU) patients and predictive value of Neutrophil Gelatinase-Associated Lipocalin (NGAL) measured at the admission in mortality of SA-AKI and non SA-AKI. Patients and Methods: A study of 101 consecutive adult patients admitted to the Intensive Care Unit (ICU) diagnosed as AKI in which there were 60 patients with SA-AKI. Acute kidney injury was defined based on Acute Kidney Injury Network (AKIN) criteria. Serum NGAL was measured using the BioVendor Human Lipocalin-2/NGAL ELISA with blood sample taken at admission. Results: Incidence of septic acute kidney injury was 59.4%, incidence of death patients reached 20.0%. Mean concentration of serum NGAL in death group was 633.56 ng/ml, higher significantly than that of survival patients (328.84 ng/ml), p&lt;0.005. Serum NGAL in non SA-AKI patients showed a better prognostic value to predict hospital mortality than that in SA-AKI patients (AUC: 0.894 and 0,807 respectively; p &lt; 0.005) Conclusion: In SA-AKI patients, serum NGAL and mortality rate increased along with the stage of AKI. Serum NGAL, measuring at admission time, was a good prognostic biomarker of mortality in both SA-AKI and non SA-AKI patients.