Accuracy Of Neutrophil Gelatinase-associated Lipocalin Research Articles

Accuracy of NGAL as a Biomarker for Urinary Tract Infection in Young Febrile Children: An Individual Patient Data Meta-Analysis

To compare the accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and leukocyte esterase (LE) for the diagnosis of urinary tract infection (UTI) in children. We performed a systematic review and individual patient data meta-analysis of studies that examined urine NGAL as a marker of UTI in children <18years of age. We created a standardized definition of UTI and applied it to all included children. We compared sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of NGAL with LE. We included individual patient data from 3 studies for a total of 845 children. Included children had a mean age of 0.9years (SD, 0.6years). Using a cutoff of 32.7ng/mL, NGAL had a sensitivity of 90.3% (95% CI: 83.2%-95.0%) and specificity of 93.7% (95% CI: 91.7%-95.4%) for the diagnosis of UTI. LE, using a cutoff of ≧ trace had a sensitivity of 81.1% (95% CI: 72.5%-87.9%) and specificity of 97.0% (95% CI: 95.4%-98.1%). The AUC for NGAL was 0.95 (95% CI: 0.92-0.98). The AUC for LE was 0.90 (95% CI: 0.86-0.93). In young, febrile children, urinary NGAL is more sensitive for the diagnosis of UTI than LE but is slightly less specific.

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study.

BACKGROUND Delayed graft function (DGF) caused by ischemia-reperfusion injury is a common pathophysiological process that should be monitored by specific biomarkers in addition to serum creatinine. Thus, this single-center retrospective study aimed to investigate the association between levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18) in DGF associated with acute kidney injury in kidney transplant recipients (KTRs) and estimated glomerular filtration rate (eGFR) at 3 years post-transplant. MATERIAL AND METHODS A total of 102 KTRs [14(13.7%) of DGF and 88(86.3%) of NON-DGF] were enrolled. DGF was defined as "dialysis is needed within 1 week after kidney transplantation". NGAL, KIM-1, L-FABP, and IL-18 were obtained from perfusate samples of donation-after-cardiac-death (DCD) kidneys, and measured by ELISA. RESULTS Compared to the NON-DGF group, KTRs in the DGF group had a statistically significant increase in levels of NGAL (P<0.001) and KIM-1 (P<0.001). Multiple logistic regression analyses showed that NGAL (OR=1.204, 95% CI 1.057-1.372, P=0.005) and KIM-1 (OR=1.248, CI=1.065-1.463, P=0.006) could be regarded as independent risk factors. The accuracy of NGAL and KIM-1 was 83.3% and 82.1%, respectively, calculated using the area under the receiver operating characteristic curve. Furthermore, the eGFR at 3 years post-transplant had a moderate negative correlation with NGAL (r=-0.208, P=0.036) and KIM-1 (r=-0.260, P=0.008). CONCLUSIONS Our results support those from previous studies showing that perfusate levels of NGAL and KIM-1 are associated with DGF in KTRs and also with reduced eGFR at 3 years post-transplant.

Diagnostic accuracy of neutrophil gelatinase-associated lipocalin as a predictor of chronic kidney disease

Introduction Chronic kidney disease (CKD) is a major threat to public health problem, in terms of prevalence of disease, cost of treatment, and the comorbidities involved. To screen out the severe disease earlier and more accurately, estimated glomerular filtration rate (eGFR) and albuminuria are still regarded as the ideal markers of kidney function. Neutrophil gelatinase-associated lipocalin (NGAL) is a new biomarker for detecting early kidney damage. The aim of the study was to assess diagnostic significance of NGAL in early stages of CKD among patients. Patients and methods We measured urinary neutrophil gelatinase-associated lipocalin (uNGAL) and serum neutrophil gelatinase-associated lipocalin (sNGAL) levels in 40 patients with stages 2 and 3 CKD and 20 controls by ELISA. Results There was a highly significant increase in uNGAL and sNGAL, albumin/creatinine ratio, and eGFR on comparison of all patients and groups 1 and 2 with the control group (P

Diagnostic relevance of neutrophil gelatinase-associated lipocalin in early detection of acute kidney injury

Objective: To evaluate the predictive and diagnostic accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in acute kidney injury (AKI) and also to predict the renal replacement therapy (RRT) using NGAL as a marker. Methods: This prospective study was conducted among the patients admitted to intensive care units. Plasma samples were collected 24 hours after admission and NGAL was measured using Triage® NGAL test, a specific point of care test which is based on the mechanism of fluorescence immunoassay. The diagnostic accuracy of plasma NGAL (pNGAL) to predict AKI in critically ill patients of ICU was assessed by applying receiver operator curve (ROC) analysis and calculating the area under the curve (AUC). Results: In this study, 100 patients with the mean age of 49.56±19.2 years were included for the period of 18 months. The blood samples were withdrawn from the patients 24 and 44 hours after admission. Totally, 55% (n=55) of ICU patients were diagnosed with AKI. Plasma NGAL level was significantly increased in AKI patients as compared to non-AKI patients (742.65±734.72 vs. 255.62±440.09 μg/L; P&lt;0.01). The sensitivity and specificity of NGAL for diagnosing AKI was 83.6% and 88.9%, respectively. The overall diagnostic accuracy was 86%. Diagnostic accuracy of NGAL for requirement of RRT was 51%. Conclusion: Plasma NGAL is a reliable marker for patients with AKI in ICU, in case the cause of kidney injury is not known. In addition, NGAL also predicts the RRT need based on AKI severity.

Pre and post analytical pitfalls of new biomarkers predicting acute kidney injury. Neutrophil gelatinase-associated lipocalin and cell cycle arrest proteins variability in urinary testing

Introduction. In the last years, many improvements were made to know better in laboratory medicine the total testing process (TTP) including the pre and post analytical phases. To date, however, laboratory common protocols do not extensively applied for the routine testing. Issue is worse for new potential biomarkers in clinical practice owing to timeliness of market entry and the urgent need to adopt new diagnostic tools. Our work conducted to investigate diagnostic pitfalls of new acute kidney injury (AKI) biomarkers with specific observations on the pre/post analytical features of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinase 2▪insulin-like growth factor binding protein 7 (TIMP-2)▪(IGFBP-7). Material and Methods. We analysed from previous two studies the urinary samples collected in intensive care unit (ICU) from an adult population undergoing cardiac surgery. Diagnostic accuracy of NGAL and (TIMP-2)▪(IGFBP-7) was determined on urinary samples. For NGAL biomarker the evaluation of two consecutive testing results was introduced. We performed measurements using a chemiluminescent method on an automatic analytical platform and a point of care testing (POCT) Nephrocheck meter. Analysis of biochemical results was performed without and with the urine creatinine (uCrea) correction. Furthermore, a method to calculate the mean variation rate was applied for different biomarker concentrations using differential equations. Results. A received operating curve for predicting AKI was obtained with AUC value= 0.66 corresponding to the better cut-off= 29 ng/mL (p=0.016). A significant association between the NGAL increase and AKI severity was achieved (p=0.02). NGAL increases showed: NGAL pre=18.3 (7.7-23.7) ng/mL, NGAL post= 19.2 (3.8-86) ng/mL median (interquartile range) statistically not significant. Analyzing the corresponded urinary creatinine (N=41), we highlighted that 38/41 had uCrea≤ 50mg/dL suggesting a possible dilution of patient samples collected. Nephrocheck AKI score cut-off=0.3, used in clinical studies, does not evaluate biomarker increase pre/post-surgery. Correction with the urinary creatinine does not have added significant outcomes. However, measure unit of (TIMP-2)▪(IGFBP-7) expressed as AKI score (ng/mL) 2 /1000 introduces a variation due to the amplification of TTP errors. Differential equations applied to Nephrocheck test results demonstrated a mean variation rate that rises as the biomarker concentration increases. Conclusions: NGAL results on urinary testing had a poor diagnostic accuracy probably due to pre-analytical variability in ICU critical patients. Pre and Post-analytical variability affected Nephrocheck results as suggested by the non-linear expression of measurements. In addition, the too tight and low AKI score reference range (0.02-0.3) may determine possible overlap between different patient groups.

Serum levels of neutrophil Gelatinase associated Lipocalin (NGAL) predicts hemodialysis after coronary angiography in high risk patients with acute coronary syndrome

BackgroundContrast-induced nephropathy (CIN) following a percutaneous coronary intervention (PCI) is the third most common cause of acute kidney injury (AKI) worldwide. Patients who require hemodialysis secondary to CIN have an elevated mortality rate as high as 55%. The current definition of CIN is based on an elevation of creatinine and decrease in urinary output. Creatinine typically increases 48 h after the contrast exposure, which delays the diagnosis and treatment of CIN. The neutrophil gelatinase associated lipocalin (NGAL) has emerged as a sensitive and specific biomarker of renal injury. Limited data exists about the effectiveness of NGAL to predict CIN in high-risk patients with acute coronary syndrome (ACS) that underwent PCI. The primary aim of this study was to determine the association of serum NGAL levels and the need for hemodialysis after PCI.MethodsThis is a prospective, observational study. NGAL levels were measured using ELISA. Blood samples were obtained within the first 6 h of hospital admission, and 12 and 24 h after contrast exposure from angiography. The primary outcome was the requirement of hemodialysis. The non-parametric Mann-Whitney U test was used to test for differences in median serum levels of NGAL. A receiver operating characteristic (ROC) curve was developed to assess the accuracy of NGAL to predict the need for hemodialysis after PCI.ResultsA total of 2875 were screened; however, 45 patients with ACS that underwent PCI were included. All patients were at high risk of developing CIN defined by Mehran score > 11 points. The median (IQR) serum concentration of NGAL was significantly higher in patients that required versus did not require hemodialysis (340 [83–384] vs. 169 [100–210], p = 0.01). Elevated serum levels of NGAL with a cut-off at 6 h post PCI of 281 mg/dL predicted the need for hemodialysis with an area under the curve of 0.86 (95% CI, 0.66–1.00).ConclusionsIn patients with ACS undergoing PCI; and high risk of developing CIN, an elevated serum level of NGAL 6 h after contrast exposure predicts the development of acute kidney injury requiring hemodialysis.

Diagnostic Accuracy of Neutrophil Gelatinase-Associated Lipocalin for Predicting Early Diabetic Nephropathy in Patients with Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Currently, there is a lack of prediction markers for diabetic nephropathy (DN) in patients with type 1 and type 2 diabetes mellitus (T1DM/T2DM). The aim of this systematic review and meta-analysis was to evaluate the value of a promising biomarker, neutrophil gelatinase-associated lipocalin (NGAL), in both serum and urine for the diagnosis of early DN in T1DM and T2DM patients with different stages of albuminuria. A comprehensive search was performed on PubMed by 2 reviewers until September 2018. Studies in which (a) the degree of DN was determined according to the urinary albumin/creatinine ratio and (b) NGAL was measured in healthy individuals and in diabetes patients with DN were included in the meta-analysis. For each study, a 2 × 2 contingency table was formulated. Sensitivity, specificity, and other estimates of accuracy were calculated using a bivariate random effects model. The hierarchical summary ROC method was used to pool data and to evaluate the area under the curve (AUC). The sources of heterogeneity were explored by subgroup analysis. Publication bias was assessed using the Deeks test. The meta-analysis enrolled 22 studies involving 683 healthy individuals and 3249 patients with diabetes, of which 488 were T1DM and 2761 were T2DM patients. Overall, pooled sensitivity and specificity among the different settings analyzed ranged from 0.42 (95% CI, 0.22-0.66) to 1.00 (95% CI, 0.99-1.00) and 0.72 (95% CI, 0.62-0.80) to 0.98 (95% CI, 0.50-1.00) in T2DM patients, respectively. For T1DM patients, the corresponding estimates were 0.71 (95% CI, 0.59-0.81) to 0.89 (95% CI, 0.64-0.97) and 0.72 (95% CI, 0.62-0.80) to 0.79 (95% CI, 0.67-0.87). The AUC of NGAL for T2DM patients ranged from 0.69 (95% CI, 0.65-0.73) to 1.00 (95% CI, 0.99-1.00) in the different settings. The results of this meta-analysis suggest that NGAL in both serum and urine can be considered a valuable biomarker for early detection of DN in diabetes patients.

Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C in Early Detection of Pediatric Acute Kidney Injury; a Diagnostic Accuracy Study.

There is a controversy regarding accuracy of neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C in early detection of acute kidney injury (AKI). The present study aimed to compare the diagnostic value of two biomarkers in this regard. In the present diagnostic accuracy study, all children between the ages of 1 month to 14 years were entered. Pediatric Risk, Injury Failure, Loss, End-stage renal disease (pRIFLE) criteria was used for identification of children with AKI as the reference test. Blood samples were taken from all patients at baseline and 48 hours after admission to assess serum creatinine and Cystatin C level. In addition, a urine sample was obtained within 6 hours of admission in order to measure NGAL level. In the end, area under the receiving operating characteristics (ROC) curve, sensitivity, and specificity of urine NGAL (uNGAL) and Cystatin C in early detection of AKI were compared. Data from 96 children with the mean age of 27.31±36.24 months were entered (56.25% girls). Area under the ROC curve of uNGAL level in diagnosis of AKI in children was 0.91 (95% CI: 0.80 to 1.00) and area under the ROC of Cystatin C was 0.90 (95% CI: 0.77 to 1.00). Both tests had the same value in diagnosis of AKI (p=0.89). The best cut-off point of uNGAL for diagnosing AKI was 125 mg/L. uNGAL had a sensitivity and specificity of 0.92 (0.62 to 0.99) and 0.69 (0.57 to 0.78), respectively. The best cut-off point of serum Cystatin C level was 0.4 mg/L. Cystatin C had a sensitivity and specificity of 0.92 (0.62 to 0.99) and 0.64 (0.52 to 0.74), respectively. The present study showed that uNGAL level has the same value as serum Cystatin C level in early diagnosis of AKI.

Accuracy of neutrophil gelatinase-associated lipocalin for acute kidney injury diagnosis in children: systematic review and meta-analysis.

To estimate the accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a biomarker for acute kidney injury (AKI) in children. A systematic review of the literature was performed. The review protocol was registered at PROSPERO (CRD 42015024153). We conducted searches in the following databases: Medline (PubMed), LILACS (BVS), SCOPUS (Elsevier), Embase (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, and ISI Web of Science, from January 1990 to October 2016. For inclusion, studies measured NGAL levels in plasma and urine for AKI in children. For each study, 2×2 contingency tables were developed. For statistical analysis we calculated the sensitivity, specificity and diagnostic odds ratio. For methodological assessment, we used Quality Assessment of Diagnostic Accuracy Studies-2. Software used for analysis was Stata 14, and RevMan 5.3. In total 13 studies were analyzed, which included 1629 children. For urinary NGAL, the pooled sensitivity was 0.76 (95% CI 0.62-0.85) and a pooled specificity 0.93 (95% CI 0.88-0.96). The diagnostic odds ratio (DOR) for the detection of AKI was 43 (95% CI 16-115) and the Area under the curve (AUC) was 0.94 (95% CI 0.92-0.96). For plasma NGAL the combined sensitivity was 0.80 (95% CI 0.64-0.90) and a combined specificity was 0.87 (95% CI 0.74-0.94). The DOR was 26 (95% CI 8.0-82) and AUC was 0.90 (95% CI 0.87-0.94) for the detection of AKI in children. The data suggest that NGAL levels can be an important biomarker for the early detection of AKI in children.

Plasma and urine neutrophil gelatinase-associated lipocalin in the diagnosis of new onset acute kidney injury in critically ill patients.

IntroductionNeutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a useful early diagnostic biomarker of acute kidney injury (AKI) where the timing of the insult is certain. However, NGAL is not well validated in adult critical care practice because of indeterminate timing of injury. Therefore, we sought to establish the predictive ability of both urine and plasma NGAL to detect AKI in ICU patients.MethodThis prospective observational study was performed in a busy large district general hospital mixed surgical-medical ICU in Reading, UK. Consecutive adult admissions to the ICU, with absence of chronic kidney disease, renal transplant or AKI as defined by RIFLE criteria were included. Blood and urine specimens were collected at admission and every 24 hours until 72 hours and tested for NGAL. The purpose of the study was to assess whether urinary NGAL (uNGAL) or plasma NGAL (pNGAL) can predict the occurrence of AKI at an earlier point of time than the conventional markers, that is creatinine and urine output as is used in RIFLE criteria.ResultsOver a 12-month period, 194 patients were enrolled. In total, 59 (30.4%) patients developed AKI. The admission pNGAL and uNGAL were significantly higher in the patients who developed AKI compared to the non-AKI patients (436 ng/mL (240, 797) versus 168 ng/mL (121.3, 274.3) P <0.001 and 342 ng/mL (61.5, 1,280) versus 34.5 ng/mL (11.5, 107.75) P <0.001 respectively). Hospital mortality was higher in the AKI group (17% versus 4%). Plasma NGAL performed fairly on admission (AUROC 0.77) and thereafter performance improved at 24 and 48 hours (AUROC 0.88 and 0.87) following ICU admission. Urine NGAL had a fair predictive value on admission (AUROC 0.79) and at 24 hours (AUROC 0.78) and was good at 48 hours (AUROC 0.82).ConclusionsIn critically ill patients without pre-existing kidney disease, both pNGAL and uNGAL measured at admission can predict AKI (defined by RIFLE criteria) occurrence up to 72 hours post-ICU admission and their performance (AUROC) was fair. The accuracy of NGAL appeared to improve slightly as patients progressed through their ICU stay. Serial measurements of NGAL (both pNGAL and uNGAL) may be of added value in an ICU setting to predict the occurrence of AKI.

Accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Diagnosis and Prognosis in Acute Kidney Injury: A Systematic Review and Meta-analysis

Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker for the early diagnosis of acute kidney injury (AKI); however, a wide range in its predictive value has been reported. Meta-analysis of diagnostic test studies using custom-made standardized data sheets sent to each author. Different clinical settings of AKI. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of NGAL to predict AKI. Plasma/serum and urine NGAL within 6 hours from the time of insult (if known) or 24-48 hours before the diagnosis of AKI if the time of insult was not known. The primary outcome was AKI, defined as an increase in serum creatinine level > 50% from baseline within 7 days or contrast-induced nephropathy (creatinine increase > 25% or concentration > 0.5 mg/dL in adults or > 50% increase in children within 48 hours). Other outcomes predicted using NGAL were renal replacement therapy initiation and in-hospital mortality. Using a hierarchical bivariate generalized linear model to calculate the diagnostic odds ratio (DOR) and sample size-weighted area under the curve for the receiver-operating characteristic (AUC-ROC), we analyzed data from 19 studies and 8 countries involving 2,538 patients, of whom 487 (19.2%) developed AKI. Overall, the DOR/AUC-ROC of NGAL to predict AKI was 18.6 (95% CI, 9.0-38.1)/0.815 (95% CI, 0.732-0.892). The DOR/AUC-ROC when standardized platforms were used was 25.5 (95% CI, 8.9-72.8)/0.830 (95% CI, 0.741-0.918) with a cutoff value > 150 ng/mL for AKI compared with 16.7 (95% CI, 7.1-39.7)/0.732 (95% CI, 0.656-0.830) for "research-based" NGAL assays. In cardiac surgery patients, the DOR/AUC-ROC of NGAL was 13.1 (95% CI, 5.7-34.8)/0.775 (95% CI, 0.669-0.867); in critically ill patients, 10.0 (95% CI, 3.0-33.1)/0.728 (95% CI, 0.615-0.834); and after contrast infusion, 92.0 (95% CI, 10.7-794.1)/0.894 (95% CI, 0.826-0.950). The diagnostic accuracy of plasma/serum NGAL (17.9 [95% CI, 6.0-53.7]/0.775 [95% CI, 0.679-0.869]) was similar to that of urine NGAL (18.6 [95% CI, 7.2-48.4]/0.837 [95% CI, 0.762-0.906]). We identified age to be an effective modifier of NGAL value with better predictive ability in children (25.4 [95% CI, 8.9-72.2]/0.930 [95% CI, 0.883-0.968]) compared with adults (10.6 [95% CI, 4.8-23.4]/0.782 [95% CI, 0.689-0.872]). NGAL level was a useful prognostic tool with regard to the prediction of renal replacement therapy initiation (12.9 [95% CI, 4.9-33.9]/0.782 [95% CI, 0.648-0.917]) and in-hospital mortality (8.8 [95% CI, 1.9-40.8]/0.706 [95% CI, 0.530-0.747]). Serum creatinine level was used for AKI definition. NGAL level appears to be of diagnostic and prognostic value for AKI.