Serum Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Neutrophil gelatinase-associated lipocalin as a biomarker for predicting acute kidney injury during off-pump coronary artery bypass grafting.

Background:Acute kidney injury (AKI) following cardiac surgery is a major complication resulting in increased morbidity, mortality, and economic burden. In this study, we assessed the usefulness of estimating serum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker in predicting AKI in patients with stable chronic kidney disease (CKD) and undergoing off-pump coronary artery bypass grafting (OP-CABG).Patients and Methods:We prospectively studied sixty nondialysis-dependent CKD patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 who required elective OP-CABG. Patients were randomized into two groups, Group D received dopamine infusion at 2 μg/kg/min following anesthesia induction till the end of the surgery and Group P did not receive any intervention. Serum creatinine, NGAL, brain natriuretic peptide, and troponin-I were estimated at specified intervals before, during, and after surgery. The results of the study patients were also compared to a simultaneous matched cohort control of thirty patients (Group A) without renal dysfunction who underwent OP-CABG.Results:No patient required renal replacement therapy, and no mortality was observed during perioperative and hospitalization period. Six patients from control group (n = 30), ten patients from placebo group (n = 30), and 12 patients from dopamine group (n = 30) developed stage 1 AKI. However, we did not observe any stage 2 and stage 3 AKI among all the groups. There was a significant increase in serum NGAL levels at the end of surgery and 24 h postoperatively in placebo and dopamine groups as compared to the control.Conclusion:The measurement of NGAL appears to predict the occurrence of AKI after OP-CAB surgery. However, large multicentric studies may be required to confirm the findings of this study.

The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women.

Circulating neutrophil gelatinase-associated lipocalin (NGAL) is associated with obesity-related metabolic disorders. This study investigated the relationship between serum NGAL and early alteration of metabolic parameters in non-diabetic Korean women, particularly with respect to saturated fat (SFA) intake. Anthropometric parameters, fasting glycemic status, and levels of lipids, oxidative stress/inflammatory markers, and NGAL were measured in 82 non-diabetic Korean women [Super-healthy group (n=57) with 0 metabolic syndrome risk factor (MetS RF) and MetS-risk group (n=25) with MetS RF≥1]. Age, weight, waist circumference, blood pressure, fasting glucose, HbA1C, triglyceride, LDL and total-cholesterol, and NGAL levels were higher, and HDL-cholesterol was lower in the MetS-risk group than in the Super-healthy group. Age-adjusted serum NGAL levels were higher in the MetS-risk group than in the Super-healthy group. NGAL increased proportionally with increase in MetS RFs (p=0.038) and correlated positively with BMI, triglycerides, LDL- and total-cholesterol, interleukin-6, white blood cell count, and neutrophil%, and negatively with HDL-cholesterol and superoxide dismutase activity. Serum NGAL levels positively correlated with SFA intake before and after adjustment (age and BMI). Serum NGAL levels were higher in high-SFA consumers [≥7g/day, ≥7% of total calorie intake (TCI)] than in low-SFA consumers (<7g/day, <7% of TCI). Serum NGAL levels were highest in the MetS-risk group consuming higher SFA and lowest in the Super-healthy group consuming lower SFA. However, serum NGAL did not significantly differ between the low-SFA consuming MetS-risk and Super-healthy groups. The relationship between circulating NGAL and early alteration of metabolic parameters is associated with dietary SFA intake in non-diabetic Korean women.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure.

BackgroundAtrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome.Material/MethodsSerum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50).ResultsMean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001).ConclusionsPresence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction.

Serum NGAL and copeptin levels as predictors of acute kidney injury in asphyxiated neonates

BackgroundAcute kidney injury (AKI) is the most common complication of perinatal asphyxia. Recent research indicates that serum neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI, but there are the lacks of data about its use in term neonates with perinatal asphyxia.MethodsA prospective cohort study was conducted on 43 term neonates. Umbilical cord blood and 24 h after birth serum NGAL, copeptin, creatinine, and molality were measured in all asphyxiated and controls neonates.ResultsDuring the study period, 8 of asphyxiated nenates (18.6 %) suffered from AKI, while 35 newborns have no signs of AKI and 30 healthy infants. We did not observe any differences in creatinine and copeptin levels, as well as serum osmolality in all three investigated groups (AKI, no-AKI, and controls) in cord blood, and 24 h after birth. Serum NGAL levels in umbilical cord blood were significantly higher in the AKI group (174.3 ng/mL) compared with no-AKI (88.5 ng/mL, p = 0.01) and control groups (28.5 ng/mL, p < 0.001), and 24 h after birth (respectively, AKI 152.5 ng/mL vs no-AKI 74.9 ng/mL, p = 0.02 vs controls 39.1 ng/mL, p < 0.001). NGAL concentration showed a strong negative correlation to umbilical artery pH (Rho = −0.42, p = 0.04), base excess (Rho = −0.31, p = 0.03), and Apgar score in 1st min (Rho = −0.41, p = 0.02) and 5th min of life (Rho = −0.20, p = 0.001). ROC curve analysis demonstrated a good predictive value for NGAL levels (>140.7 ng/mL) which allows to diagnose AKI in asphyxiated patients with 88.9 % sensitivity (95 % CI 75–95 %) and 95.0 % specificity (95 % CI 76–99 %).ConclusionNGAL seems to be a promising marker, even in subclinical AKI in neonates, due to its high specificity, but copeptin did not meet expectations.

Serum neutrophil gelatinase-associated lipocalin and resistin are associated with dengue infection in adults.

BackgroundDengue is a major health problem in tropical areas, including Taiwan. Dengue virus infection affects various types of cells and results in elevation of serum inflammatory molecules. Because these molecules may be associated with dengue virus infection, the aim of this study was to identify novel molecules in febrile patients with dengue infection. In addition, we determined whether these molecules were correlated with the count of leukocytes and platelets.MethodsFebrile adults (Age >18 years old) who presented to the emergency department and were confirmed dengue virus infection were enrolled in this study. Serum from dengue patients and healthy controls was collected and serum level of sepsis-associated inflammatory molecules was measured by Luminex assay.ResultsElevated level of macrophage migration inhibitory factor, soluble vascular cell adhesion molecule-1, sFasL, resistin and interferon-γ were detected in patients’ serum. Higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and resistin were detected in dengue patients with normal leukocyte count and all dengue patients, respectively. Furthermore, the serum level of NGAL, but not resistin, was correlated with cell count in dengue patients.ConclusionOur results revealed that resistin and NGAL are novel dengue-associated molecules. These results may help elucidate the regulatory mechanisms of anti-dengue immune responses.

URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AND CREATININE SERUM BPH PATIENTS WITH ACUTE URINE RETENTION TO DETECT KIDNEY FUNCTION DISORDERS

Objective: The main objective of this study was to determine renal function in patients with Benign Prostate Hyperplasia (BPH) in acute urinary retention period and two weeks after catheter insertion using creatinine serum and urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) biomarker parameters.Materials &amp; Method:This is an observational co-hort study conducted in patients with BPH with acute urinary retention who came to Soetomo General Hospital, Surabaya. All the patients underwent laboratory investigation that were urinary NGAL and creatinine serum, marker of renal function.Result: The mean creatinine serum of 31 samples when retention phase was 1.6 ± 0.9 mg/dL and it decreased after 2 weeks of urinary catheter insertion (1.46 ± 0.89 mg/dL). Mean urinary NGAL level when retention phase was 308.1 ± 244.8 ng/dL, and after 2 weeks after urinary catheter insertion it decreased to 158.5 ± 123.3 ng/dL. There was significant decreasing creatinine serum and urinary NGAL levels in patients with BPH and acute urinary retention in the retention phase 2 weeks after urinary catheter insertion, with p value &lt; 0.006 and &lt; 0.0001, respectively. There was no significant correlation between the duration of retention and urinary retention volume (p&gt;0.05).Conclusion: There was a significant decreasing creatinine serum and urinary NGAL levels in patients with BPH and acute urinary retention in retention phase and two weeks after urinary catheter insertion. There was no significant correlation between the urinary NGAL and creatinine serum and the duration of retention and urinary retention volume.

The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.

Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.

Serum Neutrophil Gelatinase-Associated Lipocalin Levels In Early Detection Of Contrast-Induced Nephropathy.

The purpose of this study was to investigate the role of serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the early detection of contrast-induced nephropathy (CIN). This prospective study enrolled 74 patients undergoing abdominal tomography with contrast (1 November 2014 - 28 February 2015). Demographic properties (age and sex), symptoms and CT examination results were analysed. Sodium, potassium, urea, creatinine and NGAL levels were measured at 0th, 6th, and 72nd hours. P value < 0.05 was considered statistically significant. CIN developed in 16.2% of the study patients. The mean age was significantly higher in the patients who developed CIN (p0.05). Urea levels did not differ significantly between the groups at 0th and 6th hours (p>0.05) but was significantly higher in the patients with CIN at 72nd hour (p0.05). Creatinine level was not significantly different between the groups (p>0.05) but increased significantly over time (p>0.05). There were no significant differences between the groups with respect to NGAL levels at 0th and 72nd hours(p>0.05) whereas the group with CIN had a significantly higher NGAL level at 6th hour (p.

Neutrophil gelatinase-associated lipocalin in a triphasic rat model of adenine-induced kidney injury

The aim of this study is to investigate whether NGAL, given its advantages over traditional biomarkers, can be used to describe the dynamic characteristics of the renal tubulointerstitial insult caused by adenine. Subsequently, it will be possible to assess NGAL as a biomarker of any acute kidney injury, on top of chronic interstitial disease, if NGAL levels are stable through the chronic phase of our adenine model. Study group rats were fed an adenine diet, and control group rats were fed a regular diet only. Blood and urine samples for urea, creatinine and NGAL were drawn from each rat at the beginning of the study and after 1, 3, 4, 5, 6, 7 and 8 weeks. Kidney slices from these rats were stained with Hematoxylin-eosin (HE) and β-actin stainings. Serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio in the study group were higher than baseline and than in the control group; these differences were statistically significant in some of the intervals. Tubulointerstitial changes and adenine crystals were evident in the study group rats. In the rats fed adenine, serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio followed a triphasic pattern of kidney injury: an acute phase while on the adenine diet, a partial recovery phase after switching to the regular diet and a chronic kidney disease phase after stabilization of renal function. NGAL can serve a biomarker for acute kidney injury and possibly for chronic kidney disease in the tubulointerstitial rat model.

Neutrophil gelatinase-associated lipocalin levels during the first 48 hours of intensive care may indicate upcoming acute kidney injury

PurposeThe recognition of acute kidney injury (AKI) as early as possible is important in the intensive care unit. This study proposes that serum and urine levels of neutrophil gelatinase-associated lipocalin (NGAL) may be used for this purpose. MethodsOne hundred and seven critically ill adult patients with no previous renal failure were included. NGAL levels were measured during the first 48 hours after admission; NGAL levels were followed for 7 days and classified based on Risk, Injury, Failure, Loss, and End-Stage Renal Failure criteria. ResultsThe AKI incidence was 35.5%, and serum NGAL (sNGAL) and urinary NGAL (uNGAL) levels were higher in the AKI group. The area under the receiver operating characteristic curve was 0.76 (P<.001) for sNGAL and 0.75 (P<.001) for uNGAL. Seventy-one percent of AKI cases were observed within 48 hours, with 11 additional cases in the ensuing 7 days. The mean serum creatinine levels in the 11 patients were not different from non-AKI levels (P=.197), but the NGAL values were different, and the area under the receiver operating characteristic curve for sNGAL uNGAL was 1.00 (P=.014) and 0.93 (P=.02), respectively. ConclusionsMost AKI cases were diagnosed within the first 48 hours after admission, and NGAL was useful for predicting upcoming AKI.

Neutrophil gelatinase-associated lipocal in protein levels as an acute appendicitis biomarker in children.

ObjectiveAppendicitis is very commonly encountered in emergency clinics. There is an urgent need for early and accurate predictive biomarkers of appendicitis in order to save lives, because currently-available biomarkers are imprecise and their delayed response impairs the ability of emergency doctors and pediatric surgeons to provide timely and potentially effective therapies. This study was performed to determine whether changes in the blood levels of neutrophil gelatinase-associated lipocalin (NGAL) can help to diagnose acute appendicitis in children and distinguish acute appendicitis from abdominal pain.MethodsSixty children were enrolled and divided into three groups, with 20 patients per group: Group 1 (patients with appendicitis), Group 2 (patients with abdominal pain) and Group 3 (control). Blood NGAL levels were determined by ELISA.ResultsThe basal average serum NGAL levels were 8.2 ng/ml for Group 1, 3.9 ng/ml for Group 2, and 3.3 ng/ml for Group 3. Twenty-four and 72 h after surgery the levels were 5.1 and 2.8 ng/ml, respectively, in Group 1, 2.9 and 2.8 ng/ml in Group 2, and 2.6, 2.7 ng/ml in Group 3. Setting the cut-off point to 7 generated an area under the receiving operating curve (ROC) curve at 95 % confidence interval with 77.3 % sensitivity and 97.4 % specificity.ConclusionThese data indicate a significant difference in NGAL values between basal and postoperative measurements in appendicitis patients (p < 0.05). The ROC curve results showed that NGAL is a promising novel biomarker for the differential diagnosis of acute appendicitis from abdominal pain.

Abstract TP220: Neutrophil Gelatinase-associated Lipocalin in Patients With Acute Ischemic Stroke

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker in diagnosis and prognosis in kidney and cardiovascular disease. However, the relationship between NGAL concentration and ischemic stroke is poorly understood. Hypothesis: We investigated plasma NGAL concentration in patients with acute ischemic stroke in relation to medical history, risk factors, hematologic and biochemical tests, stroke severity and subtype. Methods: Clinical data of 139 patients who admitted to a tertiary hospital with TIA (n=17) and ischemic stroke (n=122) were collected. We evaluated the following parameters: A) Medical history and risk factors of the patients; B) Hematologic and biochemical blood test at the time of admission; C) Stroke severity which was assessed using the National Institutes of Health Stroke Scale (NIHSS); D) Stroke subtype which was decided by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Results: In our study (62% male, mean age 65 ± 14 years), median admission serum NGAL level was 75 ng/mL (interquartile range [IQR] 52-112 ng/mL). Serum NGAL level was elevated in 21 (15.1%) patients with the cutoff point of 150 ng/mL. High plasma NGAL concentrations were associated with age ( p = 0.018) and previous history of coronary artery occlusive disease ( p = 0.003). Mean NIHSS score in high NGAL group was higher than normal NGAL group (7.6 ±7.2 vs 4.4 ± 5.6, p = 0.021). We observed significant correlations between serum NGAL with C-reactive protein (spearman coefficient rho = 0.319, p &lt; 0.001), erythrocyte sedimentation rate (r = 0.410, p &lt; 0.001), creatinine (r = 0.237, p = 0.005), blood urea nitrogen (r = 0.353, p = 0.003), estimated glomerular filtration rate (r = -0.471, p &lt; 0.001), fibrinogen (r = 0.327, p &lt; 0.001) and homocysteine (r = 0.189, p = 0.032). There were no significant differences in mean serum NGAL level between TIA patients and stroke patients, and stroke subtypes by TOAST classification. Conclusions: Increased NGAL in acute ischemic stroke patients is associated with age, previous coronary artery occlusive disease history and stroke severity. Elevated plasma levels of NGAL appear to be correlated with some biomarkers associated with inflammation, coagulation and kidney dysfunction.

Klotho and S100A8/A9 as Discriminative Markers between Pre-Renal and Intrinsic Acute Kidney Injury.

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21±17.32 vs. 72.97±17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97±598.05 ng/mL vs. 685.09±111.65 ng/mL; P = 0.002 in serum; 3361.11±250.86 ng/mL vs. 741.72±101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI.

The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer.

Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker that is stored in neutrophil granules. Recent studies revealed that NGAL expression increases in tissue samples of patients with inflammatory gastrointestinal system diseases and cancers. The aim of this study was to evaluate the diagnostic and predictive significance of plasma NGAL levels in various stages of adenoma-carcinoma sequence of colorectal cancer. Materials and Methods: Eighty cases were included in the study and separated into 3 groups. "Cancer Group" consisted of 27 colorectal cancer patients who underwent curative resection, whereas 24 patients with colorectal adenomatous polyps detected by colonoscopy were classified as the "Polyp Group", and 29 patients with normal colonoscopy findings were classified as the "Control Group". The serum NGAL, CEA and CA19-9 levels and histopathology findings were determined. Results: The mean plasma NGAL levels for control group, polyp group and cancer group were found to be 91.5 ng/ml, 139.6ng/ml and 184.3ng/ml, respectively. Plasma NGAL levels were found to be significantly higher in cancer group compared to the control group (p:0.006). Plasma NGAL levels were detected statistically significant and positive correlated with tumor diameter and number of metastatic lymph nodes (p:0.047, r:%38.6 and p:0.026, r:%42.8, respectively) in cancer group. Conclusions: We are of the opinion that pre-operative plasma NGAL level is a potential diagnostic biomarker for colorectal cancer patients. Although more comprehensive studies are needed for definitive judgments, serum NGAL levels may be used as a diagnostic and/or predictive biomarker for lymph node metastasis in patients with colorectal cancer.

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.

OBJECTIVEThe aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function.METHODSWe measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration.RESULTSBaseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels.CONCLUSIONSUrinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

Serum Neutrophil Gelatinase-Associated Lipocalin Predicts Survival After Resuscitation From Cardiac Arrest.

In the first days after cardiac arrest, accurate prognostication is challenging. Serum biomarkers are a potentially attractive adjunct for prognostication and risk stratification. Our primary objective in this exploratory study was to identify novel early serum biomarkers that predict survival after cardiac arrest earlier than currently possible. Prospective, observational study. A single academic medical center. Adult subjects who sustained cardiac arrest with return of spontaneous circulation. None. We obtained blood samples from each subject at enrollment, 6, 12, 24, 48, and 72 hours after return of spontaneous circulation. We measured the serum levels of novel biomarkers, including neutrophil gelatinase-associated lipocalin, high-mobility group protein B1, intracellular cell adhesion molecule-1, and leptin, as well as previously characterized biomarkers, including neuron-specific enolase and S100B protein. Our primary outcome of interest was survival-to-hospital discharge. We compared biomarker concentrations at each time point between survivors and nonsurvivors and used logistic regression to test the unadjusted associations of baseline clinical characteristics and enrollment biomarker levels with survival. Finally, we constructed a series of adjusted models to explore the independent association of each enrollment biomarker level with survival. A total of 86 subjects were enrolled. Enrollment levels of high-mobility group protein B1, neutrophil gelatinase-associated lipocalin, and S100B were higher in nonsurvivors than survivors. Enrollment leptin, neuron-specific enolase, and intracellular cell adhesion molecule-1 levels did not differ between nonsurvivors and survivors. The discriminatory power of enrollment neutrophil gelatinase-associated lipocalin level was the greatest (c-statistic, 0.78 [95% CI, 0.66-0.90]) and remained stable across all time points. In our adjusted models, enrollment neutrophil gelatinase-associated lipocalin level was independently associated with survival even after controlling for the development of acute kidney injury, and its addition to clinical models improved overall predictive accuracy. Serum neutrophil gelatinase-associated lipocalin levels are strongly predictive of survival-to-hospital discharge after cardiac arrest.

Early Biomarkers of Renal Damage in Relation to Arterial Stiffness and Inflammation in Male Coronary Artery Disease Patients

Background/Aims: Plasma neutrophil gelatinase-associated lipocalin (NGAL), urinary liver-type fatty acid-binding protein (L-FABP) and urinary kidney injury molecule-1 (KIM-1) have emerged as promising biomarkers for both acute and chronic kidney injury that also provide prognostic value for cardiovascular morbidity and mortality. Our aim was to evaluate their relationships with arterial stiffness and inflammation in coronary artery disease (CAD) patients and in clinically healthy controls. Methods: We studied 52 patients with CAD (age 63.2 ± 9.2 years) and 41 healthy controls (age 60.1 ± 7.2 years). Urinary L-FABP and KIM-1 as well as serum NGAL, adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. Results: Urinary L-FABP and KIM-1 were independent determinants of cf-PWV for the CAD patients (R²=0.584, P<0.001) but not for the controls. Adiponectin correlated with log-KIM-1 (r=0.31, P=0.028) only for the patients, while NGAL correlated with WBC count (rho=0.29, P=0.038; r=0.35, P=0.029) and resistin (rho=0.60, P<0.001; r=0.57, P<0.001) for both the CAD and control groups, respectively. Conclusion: Our findings suggest that urinary L-FABP and KIM-1 may be independently associated with aortic stiffness in individuals with CAD.

Serum Neutrophil Gelatinase-Associated Lipocalin in Infants and Children with Sepsis-Related Conditions with or without Acute Renal Dysfunction

PURPOSETo validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury (AKI) in sepsis-related conditions and its predictive and prognostic values.PATIENTS AND METHODSThis study included 65 patients, who were clinically evaluated for sepsis, severe sepsis, or septic shock, and 20 apparently healthy served as controls. Patients were divided into two groups: Group I (AKI-sepsis): 65 newly admitted patients diagnosed as sepsis, who were further divided into three subgroups according to the severity: systemic inflammatory response syndrome, severe sepsis, and septic shock, and Group II (control group): 20 apparently healthy subjects matched for age and sex, serum creatinine and serum NGAL concentrations were estimated initially within 24 hours of admission and after 72 hours of admission in all patients and control groups.RESULTSSerum NGAL increased significantly with increasing severity of renal impairment. Receiver-operating characteristic analysis suggested that serum NGAL cutoff value of 40 ng/mL within the first 24 hours of admission is highly specific and sensitive for predicting AKI, with sensitivity of 90.9% and specificity of 75.8%.CONCLUSIONWe concluded that early measurement of serum NGAL level in sepsis can serve as a clinically useful marker for early prediction of AKI and for grading of its severity.

Serum Neutrophil Gelatinase-Associated Lipocalin and Cystatin C for Assessing Recovery of Graft Function in Patients Undergoing Living-Donor Kidney Transplantation.

Neutrophil gelatinase-associated lipocalin (NGAL) can be used as an early indicator of acute kidney injury (AKI), and cystatin C is also suggested to be an ideal marker of glomerular filtration rate (GFR), but they were not sufficiently studied in recipients without delayed graft function (DGF) after living-donor kidney transplant (LDKT). The aim of the study is to investigate whether serum NGAL and cystatin C can assess the recovery of renal function after LDKT. 49 adult patients that had undergone LDKT between January 2012 and March 2014 were prospectively enrolled. Serum creatinine, NGAL, and cystatin C were measured on day 0-7, day 10, day 14 and month 9 after transplant. Recovery of graft function was evaluated by the time needed to reach eGFR > or = 60 mL/min/1.73 in2 Poor long-term graft outcome was defined as eGFR < 60 mL/min/1.73 M2 at 9 months. No DGF was recorded. Serum NGAL level decreased to normal earlier than creatinine after transplant. Cystatin C declined rapidly, but still stayed above the normal range. Serum NGAL on day 0 (p = 0.028) and cystatin C on day 2 (p < 0.001) were independent predictors of the time for graft function recovery in multivariate analysis. Compared to recipients with fair long-term graft outcome (eGFR > 60 mL/min/1.73 m2 at 9 months), recipients with poor long-term graft outcome (eGFR < 60 mL/min/1.73 m2 at 9 months) displayed higher serum NGAL on day 2 (p = 0.045), older age (p = 0.002), longer time on dialysis (p = 0.02), and lower donor eGFR (p = 0.045). There were correlations between serum NGAL and eGFR on day 0 and day 2. Correlations between serum cystatin C and eGFR on day 0, day 2, and month 9 were all significant. Serum NGAL may be used as an early predictor of recovery of post-transplant graft function after LDKT, but may not be used for real-time assessment of GFR. At the same time, the predictive ability of serum cystatin C needs to be further assessed.

SERUM NEUTROPHIL GELATINASE - ASSOCIATED LIPOCALIN (NGAL) AS A MARKER OF TUBULOINTERSTITIAL DAMAGE IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS

Determining of serum creatinine level, glomerular filtration rate and albuminuria gives us no information about tubulointerstitial kidney damage. So it is especially important to search for non - invasive diagnostic methods that allow to diagnose early stages of tubulointerstitial kidney damage and start adequate treatment. This circumstance attempts to use neutrophil gelatinase - associated lipocalin (NGAL) to assess tubulointerstitial kidney damage in patients with chronic glomerulonephritis (CGN).&#x0D; The aim: to analyze the morphological picture of the kidneys in patients with CGN with arterial hypertension (AH) and without, to investigate the relationship between serum NGAL and histological indexes of tubulointerstitial kidney damage in CGN patients with saved renal function.&#x0D; Materials and methods. We examined 81 patients with CGN. Patients were divided into two clinical groups: CGN patients with AH, CGN without AH. We analyzed indicators of tubulointerstitial kidney damage according to vivo morphological study, level of serum NGAL.&#x0D; Conclusion: there is a correlation of varying strength between serum NGAL and indexes of tubulointerstitial kidney damage in CGN patients, strong direct relationship is found between serum NGAL and IF. Diagnostics of IF by determing ofserum NGAL is a highly sensitive and specific method with the efficiency of95.3%. Increase ofserum NGAL above 5ng/ ml indicates a high probability of the IF in CGN patients.Results. Patients with AH have more pronounced histological damage of tubulointerstitial tissue than CGNpatients without AH. Serum NGAL levels are higher in CGN patients with AH and without than in the control group. We find a correlation between serum NGAL and indicators of tubulointer - stitial kidney damage. Analysis of the diagnostic operating characteristics of interstitial fibrosis (IF) by determining of serum NGAL shows that this method is highly sensitive and specific, with an efficiency of95,3%. Constructing ofa non - linear model revealed that increase of serum NGAL level above 5 ng/ml indicates a high probability of the IF in CGN patients.