Utility Of Neutrophil Gelatinase-associated Lipocalin Research Articles

Neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory markers in schizophrenia: A comparative analysis of drug-naive schizophrenia patients, remitted patients, and healthy controls

This study aims to examine the plasma concentrations of NGAL and other inflammatory parameters, including TNF-α, IL-1β, and IFN-γ, in schizophrenia patients and healthy volunteers. It also investigates potential associations between these biomarkers and symptom severity in schizophrenia and the utility of NGAL as a potential diagnostic and monitoring biomarker for schizophrenia. The study included 49 drug-naive schizophrenia patients (DNS), 59 patients with schizophrenia in remission (REM) on antipsychotic treatment, and 58 healthy volunteers (HC). The Positive and Negative Symptoms Evaluation Scale (PANSS) was utilized to assess the severity of symptoms in schizophrenia patients. Plasma levels of TNF-α, IL-1β, IFN-γ, and NGAL were measured for all participants. NGAL levels were significantly lower in the DNS group than in HC. Significantly lower TNF-α levels were observed in both the DNS and REM groups compared to the HC group. Notably, a statistically significant positive correlation was detected between TNF-α and NGAL levels. The findings of this study are noteworthy, as they demonstrate that drug-naive individuals with schizophrenia exhibit significantly diminished levels of NGAL and TNF-α compared to healthy controls. These identified biomarkers hold promise for providing valuable insights into the complex and evolving pathophysiology of schizophrenia.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC)>0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n=49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P<.001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P<.0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P=.095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Abstract 14083: Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Cardiovascular Events in Patients With Stable Coronary Artery Disease Treated With Percutaneous Coronary Intervention

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) modulates matrix metalloproteinase-9 thereby affecting the stability of the atherosclerotic plaque. Accumulating evidence showed that high NGAL levels were independently associated with major adverse cardiac events (MACE) and mortality in patients with acute myocardial infarction (MI). However, only few studies have measured NGAL in stable coronary artery disease (SCAD) patients, and no significant prognostic predicting value between NGAL and SCAD has been established yet. Hypothesis: The aim of this study was to investigate the prognostic role of NGAL in a prospective cohort study of patients with SCAD treated with percutaneous coronary intervention (PCI). Methods: In total, 2296 SCAD patients with previous PCI were enrolled in a multi-center prospective observational study. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal MI and ischemic stroke). The secondary outcome was the occurrence of combined cardiovascular events (including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for heart failure). Results: During the mean follow-up period of 4.6 ±1.7 years, 384 patients reached the primary endpoints and 746 patients reached the secondary endpoints. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first tertile and third tertile groups (log-rank test, p&lt;0.001) in subjects categorized by NGAL levels. In multivariate Cox proportional hazard regression analysis, plasma NGAL was independently associated with MACE (adjusted hazard ratio [aHR] 1.24; 95% confidence interval [CI] 1.03-1.50, p=0.02) and the risk of developing combined cardiovascular events (aHR 1.31; 95% CI 1.14-1.51, p&lt;0.001) during follow-up. Conclusions: High plasma NGAL independently associated with the occurrence of MACE and combined cardiovascular events in SCAD patients treated with PCI.

Neutrophil gelatinase-associated lipocalin: a biochemical marker for acute kidney injury and long-term outcomes in patients presenting to the emergency department.

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

Utility of Neutrophil Gelatinase-Associated Lipocalin and Emerging Lung Injury: Correspondence.

Utility of Neutrophil Gelatinase-Associated Lipocalin and Emerging Lung Injury: Correspondence.

The Utility of Neutrophil Gelatinase-Associated Lipocalin in the Detection of Emerging Lung Injury due to Mechanical Ventilation in Children: A Preliminary Study

Objective:Lung injuries are mostly ignored in patients supported by mechanical ventilation. Neutrophil gelatinase-associated lipocalin has come into prominence as an early sensitive and highly predictive biomarker of inflammation. The purpose of the study was to assess the capability of neutrophil gelatinase-associated lipocalin in recognizing lung injuries in children requiring mechanical ventilation.Materials and Methods:This prospective case-controlled study was carried out in a tertiary pediatric intensive care unit. The entire study group consisted of a total of 45 patients, 15 in the patient group (supported by invasive mechanical ventilation) and 30 in the control group (self-breathing). Whether lung injuries developed or not was investigated by measuring serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin levels in the course of ventilation support.Results:In the patient group supported by mechanical ventilation, mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were measured as 192 ± 136.7 ng/mL and 43.7 ± 57.5 ng/mL, respectively. In the control group (self-breathing patients), mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were found as 144.8 ± 95 ng/mL and 39.3 ± 85 ng/mL, respectively. The levels of serum-neutrophil gelatinase-associated lipocalin were higher in those ventilated mechanically, compared to self-breathing patients. Although urine-neutrophil gelatinase-associated lipocalin levels were higher among mechanically ventilated patients than the controls, the difference was not statistically significant.Conclusion:Based on our study findings, we consider that neutrophil gelatinase-associated lipocalin may be a useful biomarker for emerging lung injuries due to mechanical ventilation in critically ill children and deserves to be investigated.

The Utility of Neutrophil Gelatinase-Associated Lipocalin in the Detection of Emerging Lung Injury due to Mechanical Ventilation in Children: A Preliminary Study.

Lung injuries are mostly ignored in patients supported by mechanical ventilation. Neutrophil gelatinase-associated lipocalin has come into prominence as an early sensitive and highly predictive biomarker of inflammation. The purpose of the study was to assess the capability of neutrophil gelatinase-associated lipocalin in recognizing lung injuries in children requiring mechanical ventilation. This prospective case-controlled study was carried out in a tertiary pediatric intensive care unit. The entire study group consisted of a total of 45 patients, 15 in the patient group (supported by invasive mechanical ventilation) and 30 in the control group (self-breathing). Whether lung injuries developed or not was investigated by measuring serumneutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin levels in the course of ventilation support. In the patient group supported by mechanical ventilation, mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were measured as 192 ± 136.7 ng/mL and 43.7 ± 57.5 ng/mL, respectively. In the control group (self-breathing patients), mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were found as 144.8 ± 95 ng/mL and 39.3 ± 85 ng/mL, respectively. The levels of serum-neutrophil gelatinase-associated lipocalin were higher in those ventilated mechanically, compared to self-breathing patients. Although urineneutrophil gelatinase-associated lipocalin levels were higher among mechanically ventilated patients than the controls, the difference was not statistically significant. Based on our study findings, we consider that neutrophil gelatinase-associated lipocalin may be a useful biomarker for emerging lung injuries due to mechanical ventilation in critically ill children and deserves to be investigated.

The utility of neutrophil gelatinase-associated Lipocalin (NGAL) as a marker of acute kidney injury (AKI) in critically ill patients

In current clinical practice, Serum Creatinine (SCr) is a commonly used marker for the diagnosis of acute kidney injury (AKI). Unfortunately, due to a delayed increase in SCr, it is unable to accurately estimate the timing of the injury. The purpose of this study was to assess the ability of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in critically ill adult patients. The study was conducted at the Section of Chemical Pathology, Department of Pathology& Laboratory Medicine in collaboration with Department of Anesthesiology, at Aga Khan University Hospital in Karachi, Pakistan. Subjects in the age groups of18 to 60, that were admitted into the intensive care unit (ICU) with suspected sepsis were enrolled in this study.AKI was labeled by using Risk-Injury-Failure-loss-End Stage (RIFLE) criteria. Forty-eight patients, mean age being 46.5 ± 16.3, were recruited over a nine-month period. Multiple blood samples were collected from each patient at 12 h, 24 h, and 48 h. A total of 52.1% (n = 24) of ICU patients suspected of sepsis had developed AKI. Baseline characteristics of subjects with AKI were compared to those without AKI. Statistically significant difference was noted in gender (p-value< 0.05) and pNGAL (p-value< 0.001). However, no significant differences were seen with respect to age, in patients with and without AKI. The area under the curve (AUC) at12hr was 0.82 (95% CI 0.68–0.96) with a sensitivity of 70.8% and specificity of 90.9%.While AUCs at 24 h was 0.86(95% CI 0.74–0.97) with a sensitivity of 78.5% and specificity of 88.8%. Furthermore, there was a positive correlation between pNGAL and the length of ICU stay (r = 0.98). Non-survivors or expired patients had higher median pNGAL170 (202–117) ng/ml as compared to survivors 123(170–91) ng/ml. In conclusion, pNGAL is an early predictor of AKI in a heterogeneous adult ICU population. Plasma NGAL allows the diagnosis of AKI 48 h prior to a clinical diagnosis based on RIFLE criteria. Early identification of high-risk AKI in patients may allow earlier initiation of therapies and improve patient outcome.

Utility of neutrophil gelatinase-associated lipocalin in the management of acute kidney injury: A prospective, observational study

Background:Utilization of renal biomarkers such as neutrophil gelatinase-associated lipocalin in the management of acute kidney injury may be useful as a diagnostic tool in the emergency department.Objective:The aim of this study is to determine the relationship between serum neutrophil gelatinase-associated lipocalin level and the severity of the acute kidney injury based on the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification, and to investigate the role of the serum neutrophil gelatinase-associated lipocalin level in differentiating the etiology and predicting the 30-day mortality rate and need for dialysis.Methods:This prospective, observational study was conducted from March 2015 to 2016. Adult patients with acute kidney injury in the emergency department were enrolled in the study. Demographic and clinical features such as hypovolemic state, nephrotoxic substance exposure, renal functions, and serum neutrophil gelatinase-associated lipocalin level were evaluated. After the etiology of the acute kidney injury was ascertained, the severity of the acute kidney injury was determined according to RIFLE criteria. Primary outcome was defined as the correlation between serum neutrophil gelatinase-associated lipocalin level and the severity of the acute kidney injury according to RIFLE classification. Secondary outcomes were defined as the relationship between the serum neutrophil gelatinase-associated lipocalin level and the etiology of the acute kidney injury; need for dialysis and 30-day mortality were defined as poor outcomes.Results:A total of 87 patients were included in the study. Mean serum neutrophil gelatinase-associated lipocalin levels were 380.14 ± 276.65 ng/mL in RIFLE-R, 425.80 ± 278.99 ng/mL in RIFLE-I, and 403.60 ± 293.15 ng/mL in RIFLE-F groups. There was no statistically significant relationship between the severity of acute kidney injuries and serum neutrophil gelatinase-associated lipocalin level. Initial serum neutrophil gelatinase-associated lipocalin levels in the emergency department did not indicate a statistically significant ability to predict the etiology of acute kidney injury, 30-day mortality rates, or need for dialysis.Conclusion:Initial serum neutrophil gelatinase-associated lipocalin level in the emergency department is not a determinant tool for predicting the severity, etiology, 30-day mortality rates, or need for dialysis in cases of acute kidney injuries.

Creatinine, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C in Determining Acute Kidney Injury After Heart Operations Using Cardiopulmonary Bypass.

Acute kidney injury (AKI) represents frequent complication after cardiac surgery using cardiopulmonary bypass (CPB). In the hope to enhance earlier more reliable characterization of AKI, we tested the utility of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in addition to standard creatinine for early determination of AKI after cardiac surgery using CPB. Forty-one patients met the inclusion criteria. Arterial blood samples collected after induction of general anesthesia were used as baseline, further sampling occurred at CPB termination, 2 h after CPB, on the first and second day after surgery. According to AKIN classification 18 patients (44%) developed AKI (AKI1-2 groups) and 23 (56%) did not (non-AKI group). Groups were similar regarding demographics and operative characteristics. CysC levels differed already preoperatively (non-AKI vs. AKI2; P = 0.045; AKI1 vs. AKI2; P = 0.011), while postoperatively AKI2 group differed on the first day and AKI1 on the second regarding non-AKI group (P = 0.004; P = 0.021, respectively). NGAL and creatinine showed significant difference already 2 h after CPB between groups AKI2 and non-AKI and later on the first postoperative day between groups AKI1 and AKI2 (P = 0.028; P = 0.014, respectively). This study shows similar performance of early plasma creatinine and NGAL in patients with preserved preoperative renal function. It demonstrates that creatinine, as well as NGAL, differentiate subsets of patients developing AKI of clinically more advanced grade early after 2 h, also when used single and uncombined.

Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine provides early risk stratification for adverse outcomes after cardiac surgery: a prospective observational study.

Novel biomarkers of renal injury appear inconsistent in identifying a creatinine-based diagnosis of acute kidney injury. To be clinically useful, novel acute kidney injury biomarkers should identify patients at increased risk for adverse outcomes that are a consequence of acute kidney injury earlier and with greater utility than conventional creatinine-based metrics. We sought to determine the prognostic utility of both urinary neutrophil gelatinase-associated lipocalin and varying creatinine-based metrics of renal injury at multiple time points associated with cardiac surgery. Prospective observational study. Academic medical center. Six hundred three adults undergoing cardiac surgery. Nil. Urinary neutrophil gelatinase-associated lipocalin was measured at baseline and again less than 1 hour, 3 hours, and 18-24 hours after separation from cardiopulmonary bypass. Creatinine-based metrics included a Kidney Disease: Improving Global Outcomes definition of acute kidney injury through 7 days postoperatively as well as ΔSCr-initial, defined as the incremental change in SCr from baseline to first postoperative measure. Multivariable regression determined the prognostic utility of neutrophil gelatinase-associated lipocalin and creatinine, alone and in combination, for the primary composite outcome of hospital mortality or renal replacement therapy. The primary outcome occurred in 25 patients. Adjusted for covariates ΔSCr-initial greater than or equal to 0.0 mg/dL provided early prognostic utility for the primary outcome (odds ratio, 8.9; 95% CI, 3.0-26.6), the odds ratio comparable to a creatinine-based Kidney Disease: Improving Global Outcomes definition of acute kidney injury applied over 7 days postoperatively. The upper quartile of urinary neutrophil gelatinase-associated lipocalin best predicted the primary outcome when measured 18-24 hours post-cardiopulmonary bypass (odds ratio, 18.6; 95% CI, 5.1-68.4; p = 0.001) with earlier post-cardiopulmonary bypass measures of uncertain utility. Combining both ΔSCr-initial and neutrophil gelatinase-associated lipocalin measured 3 hours after cardiopulmonary bypass provided excellent early risk stratification for the primary outcome (odds ratio, 18.3; 95% CI, 4.5-75.0). Combining urinary neutrophil gelatinase-associated lipocalin with a novel creatinine-based metric, both available soon after completion of surgery, may provide previously unavailable early and effective risk stratification for serious adverse outcomes after cardiac surgery.

Neutrophil Gelatinase-Associated Lipocalin as Early Predictor of Acute Kidney Injury After Cardiac Surgery in Adults With Chronic Kidney Failure

To assess the utility of neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury (AKI) occurring after cardiac surgery in patients with prior chronic kidney failure. Patients with preoperative creatinine clearance 60 mL • min(-1) • 1.73 m(-2) or less according to the Cockcroft-Gault formula and scheduled to undergo cardiac surgery were eligible for inclusion. The AKI was defined as an increase in plasma creatinine greater than 50% over preoperative values. Threshold values of NGAL predictive of AKI were determined using receiver operating characteristic curve analysis, and predictive value of NGAL for AKI was evaluated by logistic regression. Over a 1-year inclusion period, 166 patients were included. At 6 hours post-surgery, hypertension, occurrence of at least 1 postoperative complication, and NGAL greater than 155 ng/mL were shown to be independent predictors of AKI. NGAL greater than 155 ng/mL at 6 hours was associated with an odds ratio for risk of postoperative AKI of 7.1 [2.7 to 18]. On average, diagnosis of postoperative AKI was made 20 hours earlier using NGAL at 6 hours post-surgery as compared with a diagnosis based on a 50% increase in creatinine over baseline. The threshold for NGAL of 155 ng/mL at 6 hours had a sensitivity of 79% and specificity of 58% for the diagnosis of AKI. Earlier diagnosis of AKI post-surgery based on NGAL assessment makes it possible to initiate appropriate therapy at an earlier stage in this high-risk patient population.

Neutrophil Gelatinase-Associated Lipocalin as a Follow-Up Marker in Critically Ill Pediatric Patients with Established Acute Kidney Injury

Aim: To assess the utility of neutrophil gelatinase-associated lipocalin (NGAL) in both urine and serum as a follow-up marker for the discrimination of prerenal acute kidney injury (AKI) from intrinsic AKI in critically ill pediatric patients with established AKI at the time of patient presentation. Patients and methods: This was a prospective cohort study of a heterogeneous group of critically ill children in the pediatric intensive care unit (PICU). Serum creatinine (SCr) values were obtained daily as part of routine patient care. AKI was defined as a 50% or greater increase in SCr from baseline and classified as prerenal and intrinsic AKI. Results: A total of 32 critically ill children (mean age: 105 ± 71.7 months, 56% female) with established AKI were included to the study. Area under curve (AUC) for urine and serum NGAL to distinguish prerenal AKI from intrinsic AKI was 0.94, 95% confidence interval (CI): 0.869–1.02 (p < 0.001) and 0.86, 95% CI: 0.71–1.02 (p = 0.002), respectively. Conclusion: In a heterogeneous group of critically ill children with established AKI, we found that NGAL in both urine and serum at the time of patient presentation discriminated intrinsic AKI from prerenal AKI.

Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Mortality and Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

The aim of this study was to investigate the prognostic role of neutrophil gelatinase-associated lipocalin (NGAL) in a large population of patients with ST-segment elevation myocardial infarction. NGAL is a glycoprotein released by damaged renal tubular cells and is a sensitive maker of both clinical and subclinical acute kidney injury. New data have demonstrated that NGAL is also stored in granules of mature neutrophils, and recent data suggest that NGAL may also be involved in the development of atherosclerosis. NGAL is significantly increased in patients with myocardial infarction compared with patients with stable coronary artery disease and healthy subjects. However, the prognostic value of NGAL has never been studied in patients with myocardial infarction. We included 584 consecutive ST-segment elevation myocardial infarction patients admitted to the heart center of Gentofte University Hospital, Denmark, and treated with primary percutaneous coronary intervention, from September 2006 to December 2008. Blood samples were drawn immediately before primary percutaneous coronary intervention. Plasma NGAL levels were measured using a time-resolved immunofluorometric assay. The endpoints were all-cause mortality (n = 69) and the combined endpoints (n = 116) of major adverse cardiac events (MACE) defined as cardiovascular mortality and admission due to recurrent myocardial infarction or heart failure. The median follow-up time was 23 months (interquartile range, 20 to 24 months). Patients with high NGAL (>75th percentile) had increased risk of all-cause mortality and MACE compared with patients with low NGAL (log-rank test, p < 0.001). After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of all-cause mortality and MACE (hazard ratio: 2.00; 95% confidence interval: 1.16 to 3.44; p = 0.01 and hazard ratio: 1.51; 95% confidence interval: 1.00 to 2.30; p = 0.05, respectively). High plasma NGAL independently predicts all-cause mortality and MACE in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

Biomarker explorations in acute kidney injury: the journey continues

Determining whether an elevation in serum creatinine represents structural damage or a reversible functional change is a dilemma that clinicians encounter frequently. The emergence of kidney-specific biomarkers offers an opportunity to improve our discriminatory ability. Singer et al. provide new information on the utility of neutrophil gelatinase-associated lipocalin (NGAL) to distinguish pre-renal from established acute kidney injury. Although these results are promising, several caveats need to be considered and applied for future confirmatory studies.