Higher Neutrophil Gelatinase-associated Lipocalin Research Articles

Persistent Elevation in Urinary Neutrophil Gelatinase-Associated Lipocalin Levels Can Be a Predictor of Urinary Tract Infection Recurrence or Persistence in Women

Women commonly experience urinary tract infection (UTI) recurrence. However, there is no effective tool for predicting recurrent UTI after the first UTI episode. Hence, this study aimed to investigate potential urinary inflammatory biomarkers and specific biomarkers for predicting UTI recurrence or persistence after antibiotic treatment in women. Forty women who had a history of recurrent UTI within 1 year after the initial episode and acute bacterial cystitis were treated with broad-spectrum antibiotics for 1 week. To measure inflammatory biomarker levels, urine samples were collected at the baseline and after 1 week, 1 month, and 3 months. The levels of urinary pro-inflammatory proteins such as neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor, CXC-motif chemokine ligand (CXCL)-1, interleukin-8, CXCL-10, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha were measured using commercial kits. Seven healthy age-matched women were included as controls. The changes in urinary biomarker levels at the baseline and various time points were compared between women with and without UTI recurrence within 1 month or within 3 months after the initial antibiotic therapy. At the baseline, patients with a higher urinary white blood cell count had a significantly higher NGAL level than the controls and those with a low white blood cell count. Of the 40 patients with a history of recurrent UTI, 12 presented with UTI persistence or recurrence within 1 month and 19 within 3 months after the initial antibiotic treatment. Among the 28 patients without UTI recurrence at 1 month after treatment, 7 had UTI recurrence within 3 months. Compared with patients without UTI recurrence, those with UTI recurrence had significantly higher urinary NGAL levels at 1 week, 1 month, and 3 months after the initial treatment. This study concludes that persistent elevation in urinary NGAL levels after the initial antibiotic treatment indicated persistent bladder inflammation. Further, it could be a predictor of UTI persistence or recurrence within 1 or 3 months after the initial antibiotic treatment. Patients with a history of recurrent UTI and high urinary NGAL levels after antibiotic treatment might require a longer treatment duration to completely eradicate or prevent UTI recurrence.

Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

#668 Combined biomarker testing for the assessment of acute kidney injury among myocardial infarction patients

Abstract Background and aims The utility of different biomarkers for the prediction of acute kidney injury following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies however, very few data exist on the prognostic value of combining biomarkers. Among numerous biomarkers examined, C-reactive protein (CRP) and Neutrophil gelatinase associated Lipocalin (NGAL) stand high in their utility to assess AKI risk. The aim of this study was to assess the prognostic value of combined CRP and NGAL measurement for the assessment of the risk of AKI in reperfused STEMI patients Methods Blood samples for plasma NGAL and CRP were drawn 24 hours after admission. High NGAL and CRP were defined as values within the 4th quartile (&amp;gt;75percentile). Patients were stratified into 4 study groups: Low NGAL/Low CRP, LOW NGAL/high CRO, High NGAL /low CRP and high NGAL/high CRP. Patients were assessed for the occurrence of in-AKI based on the KDIGO criteria. Results A total of 311 patients were included (mean age 66 ± 14 years, 81% males). According to the 4 study groups, there was a stepwise increase in the proportion of AKI (9% vs. 21% vs. 40% vs. 68%; p 0.001; Fig. 1). In a multivariate regression model, compared to patients having low NGAL/low CRP we observed a graded, independent increase in the risk for AKI for low NGAL/high CRP, high NGAL/low CRP and high NGAL/high CRP(OR 2.89, p = 0.02 vs. OR 3.29, p &amp;lt; 0.001 vs. OR 17.6, p &amp;lt; 0.001 respectively, Table 1). Peak concentrations showed significant areas under the curves (AUCs) for the prediction of AKI for both CRP AUC (0.692, 95% CI 0.62-0.76) and NGAL (AUC 0.778, 95% CI 0.72-0.84). The combination of NGAL and CRP yielded a significant increase in AUC to 0.822 (95% CI 0.77 to 0.88) (combined biomarkers vs CRP: p &amp;lt; 0.001 and combined vs. NGAL: p = 0.02; Fig. 2). Conclusions In patients with reperfused STEMI, the combined assessment of NGAL and CRP provided incremental prognostic information for the prediction AKI when compared with single-biomarker measurement.

#996 Validation of peritoneal NGAL as a biomarker for peritonitis: a comparison between laboratory-base method and rapid stick test

Abstract Background and Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a protein involved in iron homeostasis, inflammation, and fibrosis. Initially discovered in human granulocytes, NGAL is found in various tissues. In renal contexts, NGAL's small size (23-25 kDa) and positive charge aid glomerular filtration and absorption in the proximal tubule. Notably, elevated NGAL levels were identified in peritoneal fluids during peritonitis in 2009, establishing it as a biomarker for early Peritoneal Dialysis (PD)-associated peritonitis diagnosis for values more than 100 μg/L. While our medical centre currently relies on the lab-based NGAL assay (NGALlab), advancements introduce the NGAL dipstick test (NGALds), offering a rapid and semi-quantitative colorimetric assessment. This study compares NGALds with NGALlab in clinical practice, assessing NGALds's potential for early peritonitis detection in PD patients' peritoneal fluid. Method This study involves a validation of diagnostic accuracy conducted through a retrospective analysis of parallel samples obtained from peritoneal effluents. Samples were collected from both healthy patients during routine analysis and from cases with suspected or confirmed peritonitis. Both NGALlab and NGALds analyses were conducted on each sample. The analysis aimed to evaluate the performance of the new NGALds by comparing it with the established NGALlab. Peritoneal NGALlab quantification employed the standard BioPorto test (BioPorto Diagnostics, Hellerup, Denmark), utilizing a particle-enhanced turbidimetric immunoassay. The novel NGALds is a rapid semi-quantitative assay that measures NGAL levels in biological fluids through colourimetric test strips, utilizing an antibody sandwich lateral flow dipstick test. NGAL values were categorized into colour-coded levels: 25 μg/L, 50 μg/L, 100 μg/L, 150 μg/L, 300 μg/L, and 600 μg/L. Statistical analyses were performed using SPSS Statistics 26.0 software. Spearman rank correlation coefficients (Rs) assessed categorical groups of NGAL values for peritoneal NGALds and NGALlab tests. A graphic comparison of these two tests was presented through a Bland-Altman plot Results Out of 301 peritoneal effluent samples, 156 were diagnosed with suspected peritonitis by ISPD Criteria. As Table 1 showed, NGALds showed a strong correlation with NGALlab categories (Rs = 0.876, P = 10−96), successfully diagnosing 96% (150 out of 156) peritonitis cases. Discrepancies between NGALlab and NGALds, visualized in the Bland-Altman plot (Fig. 1), were most notable when NGAL values exceeded the 600 μg/L threshold. However, this difference doesn't impact clinical significance, as high NGAL values remain diagnostically for peritonitis with both methods. Conclusion In conclusion, our study underscores a significant correlation between NGAL values measured by the laboratory method (NGALlab) and the NGAL dipstick test (NGALds). Importantly, NGALds exhibited a strong capability, correctly identifying 96% of peritonitis cases determined by NGALlab. Beyond statistical correlation, the NGAL dipstick emerges as a valid alternative for swift evaluation in patients presenting symptoms suggestive of peritonitis. Its ease of use, rapidity, and semi-quantitative colorimetric assessment make NGALds a patient-friendly tool. This user-friendly characteristic holds immense potential for streamlined clinical workflows, allowing for prompt and efficient peritonitis diagnosis.

Combined biomarker testing for the assessment of cardio-renal interactions among myocardial infarction patients

Abstract Funding Acknowledgements None. Background The utility of different biomarkers for the prediction of either renal or cardiovascular outcomes following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies however, very few data exist on the prognostic value of combining biomarkers. Among numerous biomarkers examined, C-reactive protein (CRP) and Neutrophil gelatinase associated Lipocalin (NGAL) stand high in their utility to assess the cardiorenal crosstalk. The aim of this study was to assess the prognostic value of combined CRP and NGAL measurement for the assessment of renal and cardiovascular outcomes in reperfused STEMI patients. Methods Blood samples for plasma NGAL and CRP were drawn 24 hours after admission. High NGAL and CRP were defined as values within the 4th quartile (&amp;gt;75percentile). Patients were stratified into 4 study groups: Low NGAL/Low CRP, LOW NGAL/high CRO, High NGAL /low CRP and high NGAL/high CRP. Patients were assessed for the occurrence of in-hospital adverse clinical events (MACE). These included occurrence of acute kidney injury , 30-day mortality and their combination. Results A total of 311 patients were included (mean age 66 ± 14 years, 81% males). According to the 4 study groups, there was a stepwise increase in the proportion of in hospital MACE ( 9% vs. 21% vs. 40% vs. 68% ;p,0.001,figure 1). In a multivariate regression model , compared to patients having low NGAL/low CRP we observed a graded, independent increase in the risk for MACE for low NGAL/high CRP , high NGAL/low CRP and high NGAL/high CRP levels( OR 2.89, p=0.02 vs. OR 3.29,p&amp;lt;0.001 vs. OR 17.6,p&amp;lt;0.001 respectively). Peak concentrations showed significant areas under the curves (AUCs) for the prediction of MACE for both CRP AUC (0.692,95% CI 0.62-0.76) and NGAL ( AUC 0.778,95% CI 0.72-0.84). The combination of NGAL and CRP yielded a significant increase in AUC to 0.822 (95% CI 0.77 to 0.88) (combined biomarkers vs CRP: p&amp;lt;0.001 and combined vs. NGAL :p=0.02,figure 2). Conclusions In patients with reperfused STEMI, the combined assessment of NGAL and CRP provided incremental prognostic information for the prediction of in hospital MACE when compared with single-biomarker measurement.Proportion of in-hospital MACEAUC CR NGAL

Environmental fluoride exposure and implications on potential pediatric kidney health risks: an approach with urinary biomarkers.

Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11-18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions.

Interaction between serum neutrophil gelatinase associated lipocalin and visceral fat area on cardiovascular health in a cohort of community-based individuals

BackgroundWe assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. MethodsThis prospective study involved 1349 adults (43.2% men) aged 50–80 y, without baseline cardiovascular diseases, from communities in 2013–2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. ResultsIn fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03–2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11–1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (Pinteraction < 0.05). ConclusionsSerum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women.

Values of serum neutrophil gelatinase-associated lipocalin and cystatin C after percutaneous coronary intervention for early diagnosis of contrast-induced nephropathy.

Serum creatinine (SCr) is not a sensitive and reliable index for the early diagnosis of acute kidney injury caused by contrast-induced nephropathy (CIN). The aim of this study was to explore the values of serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys-C) after percutaneous coronary intervention (PCI) for the early diagnosis of CIN. Three hundred patients receiving PCI from January 2018 to December 2020 were assigned to a CIN group (n=25) and a non-CIN group (n=275), respectively. SCr, Cys-C and NGAL levels were measured, and their sensitivities for early CIN diagnosis were evaluated by the area under the receiver operating characteristic curve (AUC) values. The NGAL and Cys-C levels of the CIN group began to rise 6 and 12 h after operation, respectively (P<0.05). The CIN group had higher NGAL and Cys-C levels than those of the non-CIN group 12, 24 and 48 h after operation (P<0.05). The AUC values of NGAL, Cys-C and SCr 24 h after operation were 0.885, 0.874 and 0.856, respectively. The serum NGAL and Cys-C levels of patients after PCI reflect the early changes of renal function, which are valuable for early CIN diagnosis.

B-289 Acute Kidney Injury Urinary Biomarker, Neutrophil Gelatinase-Associated Lipocalin (NGAL) Analytical Performance Evaluation on Roche Cobas c502 Chemistry Platform

Abstract Background Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KDIGO guidelines suggest serum creatinine increase as a diagnostic marker for AKI but elevation of serum creatinine levels can take up to seven days. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early tubular injury biomarker for AKI that is detected within three hours of AKI patients’ urine. In this study, we evaluated technical performance of BioPorto NGAL assay on Roche cobas c502 chemistry analyzer. Methods BioPorto’s (Hellerup, Denmark) particle enhanced turbidimetry immunoassay (PETIA) NGAL assay was installed on cobas c502 chemistry analyzer (Roche, Indianapolis, U.S.A) following vendor-specific application parameters with few modifications. Linearity was determined with BioPorto’s linearity material and verified by serial dilutions of a high NGAL patient urine sample. Limit of quantitation was determined in urine samples with values 20, 25 and 35 ng/mL, run in duplicate for 10 days. Precisions were determined by running urine samples containing 100 ng/mL and 400 ng/ml NGAL 20 times for within-run precision and twice a day × 10 days for between-run precision, respectively. To determine the accuracy of the NGAL method on cobas 502, 40 sample results (provided by the vendor) were compared with those measured on Siemens Atellica using BioPorto’s NGAL assay. Reference interval verification was carried out in 40 urine samples collected from healthy adult volunteer-donors. Results The linearity was found to be excellent from 0–3000 ng/mL. Limit of quantification was found at 26 ng/mL. Precision results are in the table below. Method comparison showed a slope of 0.90 and intercept of 32.9. The reference interval was verified to be &amp;lt;50 ng/mL (in accordance with current NGAL reference cut­off for AKI diagnosis). Conclusion Performance of BioPorto’s NGAL PETIA assay was validated in urine on cobas c502 chemistry analyzer.

Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap.

Asthma COPD overlap (ACO) is a consensus-based phenotype having characteristics of both COPD and asthma. Distinguishing ACO from other diseases is even more important as it is related to low health-related quality of life, augmented exacerbation rate and hospital admission, a rapid deterioration in lung function, and increased morbidity and mortality. But it cannot be diagnosed explicitly based on spirometry tests, patient demographics, radiology, or by-sputum cytology. There is an unmet need to develop biomarkers. To assess the role of sputum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of ACO. To find the correlation between sputum NGAL levels with forced expiratory volume 1 (FEV1) and exacerbation rate in ACO. To find the correlation between sputum NGAL level with sputum neutrophils and eosinophils in ACO. In this comparative correlational study, 180 subjects were enrolled into four groups with 45 patients each with asthma, COPD, ACO, and healthy nonsmokers respectively, respectively. After taking detailed history and demographics, sputum was analyzed for the differential count and NGAL. Asthma COPD overlap (ACO) cases had high sputum NGAL levels; the second was the COPD group, and the last in the case asthma group. Nonsmokers had notably lower readings than the diseased. Out of three, receiver operating characteristic (ROC) figures, the validity of NGAL was best in selecting patients of ACO than COPD and asthma. The area under curve (AUC) was highest for ACO and less than the acceptable limit for the remaining two. NGAL cut-off value of 2473 pg/mL had 80% sensitivity and 50% specificity for ACO. The present study investigated the sputum NGAL levels as a biomarker in ACO identified by the syndromic approach. Sputum NGAL, a biomarker associated with airway inflammation in airway diseases, was supportive of clinically differentiating ACO from asthma to COPD. How to cite this article: Babu A, Narayanswamy H, Baburao A. Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap. J Assoc Physicians India 2023;71(9):34-38.

Predictive value of elevated neutrophil gelatinase-associated lipocalin levels for assessment of in-hospital adverse outcomes among myocardial infarction patients.

Inflammatory biomarkers are known to rise and have predictive value for adverse outcomes in patients with acute coronary ischemia. One of those biomarkers is neutrophil gelatinase-associated lipocalin (NGAL). To date, only very few studies have assessed the prognostic value of NGAL in this setting. We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST-elevation myocardial infarction patients. High NGAL was defined as values within the 4th quartile. Patients were assessed for major in-hospital adverse clinical events (MACE). Multivariable logistic regression and area under the receiver operating characteristic curve (AUC) were used to further evaluate NGAL association for MACE and discrimination ability. A total of 273 patients were included. patients with high NGAL were at increased risk for MACE (62% vs. 19%; odds ratio 6.88, 95% confidence interval, 3.77-12.54, P < 0.001). After propensity score matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, P = 0.002). In multivariable regression, high NGAL level was independently associated with MACE. The discrimination ability of NGAL to identify MACE (AUC 0.823), is significantly better than that of other inflammatory markers. Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers.

Predictive value of elevated neutrophil gelatinase-associated lipocalin (NGAL) levels for assessment of in hospital adverse outcomes among myocardial infarction patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Inflammatory biomarkers are known to rise and have significant predictive value for adverse outcomes in patients with acute coronary ischemia .Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein stored in mature neutrophil granules, is significantly increased in patients with myocardial infarction compared with patients with stable coronary artery disease and healthy subjects. To date, very few studies have assessed the prognostic value of NGAL in this setting. Purpose We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI). Methods Blood samples for plasma NGAL were drawn immediately after admission. High NGAL was defined as values within the 4th quartile (&amp;gt;75percentile). Patients were assessed for major in-hospital adverse clinical events (MACE). These included reduced left ventricular ejection fraction, clinical heart failure findings and 30-day mortality. Multivariable logistic regression was used to evaluate the association between NGAL group and MACE. Receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of NGAL compared with other inflammatory biomarkers including white blood cell count(WBC), peak troponin level, peak C-reactive protein(CRP) and neutrophil/lymphocyte ratio(NLR) for the prediction of MACE. Results A total of 273 patients were included (mean age 66 ± 14 years, 81% males). Patients with high NGAL were at increased risk for MACE (62% vs. 19%; OR 6.88, 95%CI 3.77-12.54, p&amp;lt;0.001, Figure 1). After propensity score matching, 55 pairs of comparable patients were identified. Following matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, p=0.002; figure 1). In the multivariable logistic regression high NGAL level was independently associated with MACE (OR 9.25, 95%CI 4.33-19.76, P&amp;lt;0.001). The discrimination ability of NGAL to identify MACE (AUC 0.823) was significantly better (figure 2; p&amp;lt;0.001) than that of CRP (AUC 0.627), troponin (AUC 0.588), WBC (AUC 0.583) and NLR (AUC 0.601). Conclusions Among STEMI patients undergoing primary PCI, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers.

Neutrophil gelatinase-associated lipocalin as a predictor of pre-eclampsia: A systematic review and meta-analysis.

Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found an association between maternal blood and urine levels and the development of pre-eclampsia. To examine whether maternal blood and urine levels of NGAL are good predictors of pre-eclampsia. The authors searched MEDLINE databases via PubMed, Embase, Scopus, Scielo, Google Scholar, PROSPERO International Prospective Register of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The authors included case-control observational clinical studies comparing protein levels of NGAL in serum and urine in women with pre-eclampsia with uncomplicated pregnancies. Only studies where the collection of blood or urine was peformed before the occurrence of pre-eclampsia were selected. The primary outcome was the difference in NGAL levels in blood or urine between women with and without pre-eclampsia. Seven studies in total were included: five studies measuring NGAL in blood and two in urine. Regarding the serum studies, 315 patients were included as cases and 540 as controls. Higher NGAL in maternal blood during all three trimesters together was associated with pre-eclampsia; the standardized mean difference was 1.15 ng/mL (95% confidence interval, 0.92-1.39; P < 0.01). Regarding the urine studies, 39 patients were included as cases and 220 as controls. There was no statistically significant difference between patients with pre-eclampsia and controls regarding urine NGAL. NGAL in maternal blood is higher in patients who later develop pre-eclampsia compared with controls and could be used as a potential predicting test in the routine clinical setting.

Validation of Neutrophil gelatinase associated lipocalin (NGAL), a urinary biomarker for Acute Kidney Injury and the positive interference from high leukocyturia samples

Abstract Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES (KDIGO) guidelines currently suggest measuring the increase of serum creatinine as a diagnostic marker for AKI. However, the elevation of serum creatinine levels can take up to seven days or when &amp;gt;50% kidney function is lost. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for tubular injury, which can be detected in the urine of AKI patients in as early as three hours. In the current study, we evaluated the performance of BioPorto’s (Hellerup, Denmark) NGAL assay, which uses particle enhanced turbidimetry immunoassay (PETIA) technology on the Roche (Indianapolis, USA) cobas c502 chemistry analyzer. Linearity was determined using linearity material from BioPorto and also verified by serial dilutions of a high NGAL patient sample. The limit of quantitation was determined by running urine samples with values of 20 ng/mL, 25 ng/mL, and 35 ng/mL, respectively in duplicate for 10 days. Within-run precisions were determined by running urine two samples containing 100 ng/mL and 400 ng/mL NGAL 20 times and between–run precisions were determined by running the same samples 2 times a day for 10 days. To determine the accuracy of the NGAL method on cobas 502, 40 samples were used to compare results with those measured on Siemens Atellica using the BioPorto’s NGAL assay. Reference interval was verified in 40 urine samples collected from healthy donors. A urine dipstick test was performed to confirm the normal urine samples did not contain leukocyte esterase activity. Since NGAL is also present in neutrophils, we evaluated the effect of leukocytes in urine with the NGAL assay. Results showed the sample with 75 leukocytes/µL had an NGAL of 68 ng/mL and the sample with 500 leukocytes/µL has an NGAL of 222 ng/mL. The linearity range was determined to be 0 - 3000 ng/mL with a limit of quantification of 26 ng/mL. The within-run precision mean and CV% are 121 ng/mL, 4.3% for Level 1 and 401 ng/mL, 1.8% for Level 2. Between-run precisions mean and CV% are 106 ng/mL, 4.8% for Level 1 and 399 ng/mL, 2.6% Level 2. Method comparison had a slope of 0.90 and an intercept of 32.9. The reference interval was determined to be &amp;lt;50 ng/mL and Leukocytes in urine did cause false-positive NGAL results.

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.

Predictive and Prognostic Value of Serum Neutrophil Gelatinase-Associated Lipocalin for Contrast-Induced Acute Kidney Injury and Long-Term Clinical Outcomes after Percutaneous Coronary Intervention.

Neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an early marker for estimating the risk of contrast-induced acute kidney injury (CI-AKI). However, the predictive value of baseline serum NGAL levels for CI-AKI remains unclear. Serum NGAL was measured before percutaneous coronary intervention in 633 patients with coronary artery disease. The primary clinical endpoints were a composite of major adverse cardiac and cerebrovascular events (MACCEs; cardiac death, myocardial infarction, stroke, and any revascularization). The mean follow-up duration was 29.4 months. Ninety-eight (15.5%) patients developed CI-AKI. Compared with patients without CI-AKI, baseline serum NGAL was higher in patients with CI-AKI (149.6 ± 88.8 ng/mL vs. 138.0 ± 98.6 ng/mL, p = 0.0279), although serum creatinine and estimated glomerular filtration rate were not different between groups. Patients in the highest tertile of baseline serum NGAL showed a significantly higher rate of MACCEs (10.5% vs. 3.8%, p = 0.02). Using the first tertile as a reference, the adjusted hazard ratios for MACCEs in patients in the second and third tertiles of NGAL were 2.151 (confidence interval (CI) 0.82 to 5.59, p = 0.116) and 2.725 (CI 1.05 to 7.05, p = 0.039), respectively. Baseline serum NGAL is a reliable marker for predicting CI-AKI, and high serum NGAL levels are associated with a higher incidence rate of long term MACCEs.

Relation of neutrophil gelatinase-associated lipocalin (NGAL) levels and in-hospital outcomes of ST-segment elevation myocardial infarction patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive maker of both clinical and subclinical acute kidney injury (AKI). This glycoprotein is also stored in granules of mature neutrophils and is significantly increased in patients with myocardial infarction compared with patients with stable coronary artery disease or healthy subjects. Only limited data is present however, regarding the prognostic implications of NGAL in myocardial infraction patients. Purpose We evaluated the possible relation between NGAL levels and in-hospital outcomes in ST elevation myocardial infarction (STEMI) patients. Methods We included 267 patients with STEMI treated with primary coronary intervention. Blood samples for plasma NGAL were collected 24 hours following PCI. We assessed the relation of high serum NGAL, defined as values within the upper tertile (&amp;gt; 66th percentile) and various parameters including left ventricular ejection fraction, AKI, In-hospital adverse events (heart failure symptoms, need for inotropes or 30-day mortality) as well as 30-day mortality alone. Results Patients having high NGALs levels (n=89) were more likely to have LVEF &amp;lt; 45% (40% vs. 25%, p=0.009), AKI (43% vs. 4.5%, P&amp;lt;0.001), a composite of in-hospital adverse outcomes (58% vs. 39%, p=0.003) and 30-day mortality (4.5% vs. 0.6%, p=0.04). High NGAL levels were also associated with longer hospital stay and C-reactive protein levels. In a multivariate regression model high NGAL levels were independently associated with in-hospital adverse outcomes (OR 2.03, 95%CI: 1.19 - 3.46, p=0.009). Conclusions Elevated NGAL levels suggesting increased inflammation are common among STEMI patients and may be a marker of adverse outcomes.

Predictive Value of Elevated Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels for Assessment of Cardio-Renal Interactions among ST-Segment Elevation Myocardial Infarction Patients.

Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients treated with primary coronary intervention (PCI). Methods: We performed a prospective, observational, open-label trial. High NGAL was defined as values within the third tertile (>66 percentile). Results: A total of 267 patients were included (mean age 66 ± 14 years, 81% males). Short-term adverse outcomes were consistently increased in the high NGAL group with more acute kidney injury, lower mean left ventricular ejection fraction, higher 30-day mortality, and higher incidence for the composite outcome of major adverse cardiac events (MACE). In a multivariate logistic regression model, high NGAL emerged as a strong and independent predictor for MACE (OR 2.07, 95% CI 1.15–3.73, p = 0.014). Conclusions: Among STEMI patients undergoing primary PCI, elevated NGAL levels are associated with adverse renal and cardiovascular outcomes, independent of traditional inflammatory markers. Further studies are needed to assess the potentially unique role of NGAL in cardio–renal interactions.

Prognostic utility of neutrophil gelatinase associated lipocalin in cardiac ICU: A prospective study

Our study aims to evaluate the role of neutrophil gelatinase associated lipocalin (NGAL) as an early surrogate marker in predicting acute kidney injury (AKI) and mortality in cardiac ICU patients. The study was conducted at SRN Hospital, excluding those with known renal diseases. Out of 152 patients, 56 developed AKI (cases) and 96 were our controls. Higher NGAL was associated with increased mortality rates (P = 0.0201 and 0.0255 for serum and urinary NGAL respectively). Our study concluded that NGAL measurement at admission may be a boon in improving the outcome of cardiac ICU patients.

Neutrophil gelatinase associated lipocalin in predicting postoperative acute kidney injury in elderly.

Elderly patients are at increased risk of developing acute kidney injury (AKI) following major surgery and rapid diagnosis is essential. This study aimed to examine the potential utility of plasma neutrophil gelatinase associated lipocalin levels in early prediction of AKI in geriatric patients undergoing laparotomic oncological surgery. This prospective single-center cohort study included 60 geriatric patients (≥ 65years of age) that underwent major oncologic surgery with laparotomy. Perioperative measurements of plasma creatinine, blood urinary nitrogen, plasma lactate, urine output, and neutrophil gelatinase associated lipocalin (NGAL) were made. Patients were followed for AKI development, which is the primary outcome measure, and predictive role of NGAL was investigated. At 48h follow-up, AKI developed in 13 patients (21.7%). Significant differences in creatinine (p < 0.001), NGAL (p < 0.001), and urine output levels (p = 0.001) were evident over time between the two groups. High NGAL measurements at 6 and 24h after surgery seem to be highly predictive of AKI development. At 6h, a plasma NGAL level greater than 71.8ng/mL has a sensitivity and specificity of 85% and 81% in predicting subsequent AKI development. Plasma NGAL levels seem to represent an early and reliable marker for AKI in elderly patients undergoing laparotomic surgery with the potential to allow early diagnosis and prevent further renal deterioration. Further confirmatory studies are warranted. The study was registered to ClinicalTrials.gov (number, NCT05030727). Elderly patients are at increased risk of postoperative acute kidney injury (AKI). This study shows that plasma neutrophil gelatinase associated lipocalin is a helpful marker to predict AKI in elderly patients undergoing laparotomic major surgery, which will allow early diagnosis and prevent further renal deterioration in this vulnerable patient group.