Value Of Neutrophil Gelatinase-associated Lipocalin Research Articles

#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.

#758 NGAL dipstick for peritonitis: bridging the gap between rapid assessment and clinical efficiency in peritoneal dialysis

Abstract Background and Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a versatile protein known for its multifunctional roles, extending beyond its conventional use as a biomarker. It actively participates in crucial biological processes such as inflammation, proliferation, and migration. This study seeks to evaluate NGALds, a recently developed dipstick test, in comparison to the established laboratory method (NGALlab) for the early detection of peritonitis related to peritoneal dialysis (PD). The focus of the investigation lies in analyzing peritoneal fluid to develop a rapid and effective diagnostic tool, aiming to enhance the management of peritonitis. Method A retrospective analysis was undertaken to validate diagnostic accuracy, utilizing parallel samples obtained from peritoneal effluents. Samples were obtained from both PD stable patients undergoing routine analysis and from PD patients with suspected or confirmed peritonitis. The assessment of NGALds involved a direct comparison with the established NGALlab. Peritoneal NGALlab quantification was conducted using the BioPorto test, employing a particle-enhanced turbidimetric immunoassay. The NGALds, a rapid semi-quantitative assay, utilized colorimetric test strips and an antibody sandwich lateral flow dipstick test. The greatest value of NGAL detected by dipstick is 600 μg/L. Statistical analyses, including Spearman rank correlation coefficients (Rs), were performed with SPSS Statistics 26.0 software. Additionally, ROC analysis was carried out using white cell count and percentage of Neutrophils in peritoneal fluids as the gold standard. Results Among the 301 peritoneal effluent samples analyzed, 156 were diagnosed with suspected peritonitis using NGALlab and ISPD criteria. Each sample underwent analyses with both NGALlab and NGALds. As depicted in Fig. 1, NGALds exhibited a robust correlation with NGALlab categories (Rs = 0.876, P < 0.001), accurately identifying 96% (150 out of 156) of peritonitis cases. Discrepancies between NGALlab and NGALds were most evident when NGAL values exceeded the 600 μg/L threshold. Nevertheless, these variations did not impact clinical significance, as both methods consistently diagnosed elevated NGAL values indicative of peritonitis. After ROC analysis, which yielded an AUC of 0.82 (p < 0.001) (Fig. 2), the Youden Index was employed to identify a threshold value of 100 μg/L for the diagnosis of suspected peritonitis. Importantly, the application of this threshold to NGALds demonstrated a positive predictive value of 0.64 and a negative predictive value of 0.87. Conclusion In conclusion, our study reinforces the significant correlation between NGAL values obtained through the laboratory standard (NGALlab) and the novel NGAL dipstick test (NGALds). Notably, NGALds exhibited high efficacy, accurately identifying 96% of peritonitis cases diagnosed by NGALlab. This robust performance positions the NGAL dipstick as a valuable and accessible alternative for rapid assessment in patients exhibiting symptoms indicative of peritonitis. The user-friendly attributes of NGALds not only make it a practical diagnostic tool but also a patient-centric one. Furthermore, the high negative predictive value provides confidence in considering NGALds as a frontline diagnostic tool for suspected peritonitis. The ease of use and prompt results open a promising avenue for improving clinical workflows, offering an opportunity for expedited and efficient peritonitis diagnosis. For instance, NGALds could find utility in centres where NGAL is unavailable in the laboratory or at the patient's home.

#554 Baseline neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy

Abstract Background and aims Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury (AKI). There is only limited data, however, on the optimal timing for assessment, the cut-off values and its utilization for ruling out AKI We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of AKI among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). Methods We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels. Results Mean age was 62 ± 13 years and 78% were men, and a total of 20 (15%) developed AKI. Patients with AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p < 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p < 0.001). There were no significant changes between NGAL 0 & 24 hours within the 2 groups (Fig. 1). According to the ROC curve analysis NGAL 0 performed better than NGAL 24 for AKI prediction (Fig. 2). The optimal NGAL 0 level for AKI prediction was >125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p < 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0<125 ng/mL was 94%. Conclusions Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of AKI.

#2307 Serum NGAL, MMP-9 and suPAR in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes or obesity

Abstract Background and Aims Type 1 diabetes mellitus (DM1) and obesity represent two chronic paediatric diseases with worryingly rising incidence, characterized by chronic inflammation, endothelial dysfunction and increased risk for kidney impairment and cardiovascular disease. The aim of this cross-sectional study was to explore the potential usefulness of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), Matrix Metalloproteinase-9 (MMP-9) and Soluble Urokinase Plasminogen Activator Receptor (suPAR) for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity. Method Serum samples were obtained from children and adolescents aged <18 years old with DM1 (n=35) or obesity (n=38) and normal renal function with no history of albuminuria, as well as from healthy controls (n=23). Serum NGAL, MMP-9 and suPAR concentrations were measured using commercially available sandwich ELISA kits (NGAL: (DY1757-05), MMP-9: (DMP900); suPAR: (DUP00); R&D systems). All patients were evaluated for anthropometric indices (weight, height, BMI) while for different degrees of weight status we used the body mass index (BMI) z-score adjusted for age and sex. Estimated glomerular filtration rate (eGFR) was calculated according to the revised bedside Schwartz formula. Results Serum NGAL values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with T1DM with diabetes duration (Spearman rho 0.364, p=0.044), and in all study participants with BMI z-score (Spearman rho 0.401, p=0.004). Furthermore, serum MMP-9 levels were significantly increased in patients with T1DM and in patients with obesity compared to controls. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls (Table 1). Finally, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p<0.001) and creatinine levels (Spearman rho −0.334, p=0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p=0.009). Conclusion Circulating NGAL, MMP-9 levels may prove useful as surrogate biomarkers to creatinine, GFR and albumin excretion rate for early detection of kidney injury, inflammation or endothelial dysfunction and cardiovascular complications in children and adolescents with T1DM or obesity. Children with obesity may have impaired inflammation status, kidney and endothelial function to a higher degree compared to children with T1DM, which may suggest that obesity may impose a greater health burden than T1DM, at least during childhood or the first years after T1DM diagnosis.

Admission plasma concentration of neutrophil gelatinase-associated lipocalin and -C-reactive protein have additive prognostic value in patients with STEMI

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Righospitalets Forskningsfond (07IO) Lundbeck Foundation (R186-2015-2132). Background Inflammation plays an apparent critical role in patients with acute coronary syndrome (ACS) and is associated with mortality. However, the complex process is poorly understood. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker originating from mature neutrophils and renal tubular cells. It has previously been shown to be associated with mortality and acute kidney injury in ACS patients. In this study we sought to assess the potential additive prognostic value of NGAL and its relation to other markers of inflammation. Methods In 1556 consecutive ST-elevation myocardial infarction (STEMI) patients, NGAL and C-reactive protein (CRP) plasma concentration were measured at hospital admission, before acute coronary angiography. Patients were stratified to plasma concentration of both biomarkers >/< the median concentration into 4 groups (low NGAL/ low CRP (group 1), low NGAL/high CRP (2), high NGAL/low CRP (3), high NGAL/high CRP(4)). Primary outcome was 30-day all-cause mortality. Results In total, 477 (31%), 324 (21%), 316 (20%), and 439 (28%) patients were stratified in group 1-4, respectively. With 0, 1, or 2 biomarker plasma concentration above the median (group 1 – 4), patients were older (61 – 67 years old, p<0.0001), had more comorbidity (hypertension (40 – 53%), p=0.002; previous stroke (4.0 – 9.9%), p=0.007; peripheral arterial disease (PAD) (2.6 – 10%), p<0.0001; chronic kidney dysfunction (CKD) (0.6 – 11%), p<0.0001) and more critical per-infarction circumstances (time from symptom debut to angiography (170 – 229 minutes), p<0.0001; cardiogenic shock (1.3 – 14%), p<0.0001, cardiac arrest (0.8 – 3.4%), p=0.0002) and lower left ventricular ejection fraction (LVEF) (48 – 43%, p<0.0001). Increased NGAL and CRP was associated with 30-day all-cause mortality (Figure A). Only high NGAL/high CRP was independently associated with 30-day mortality in a cox proportional hazard model when adjusting for age, hypertension, previous stroke, CKD, LVEF, and cardiogenic shock (HR (95% CI) 5.19 (1.20 – 22.52), p=0.03). Both CRP and NGAL had significant predictive value of 30-day mortality (AUC ROC 0.67, p<0.0001 and 0.78, p<0.0001, respectively). Combining NGAL and CRP did, however, not increase the predictive value of NGAL alone (AUC ROC 0.77, p=0.86) (Figure B). Conclusion Combined admission NGAL and CRP plasma concentration was independently associated with 30-day all-cause mortality in STEMI patients. Adding CRP to NGAL did, however, not increase the predictive value.Figure AFigure B

Neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy in patients undergoing primary coronary intervention

Abstract Funding Acknowledgements None. Background Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury(AKI) . We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of contrast induced AKI (CI-AKI) among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). Methods We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of CI-AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels. Results Mean age was 62 ±13 years and 78% were men, and a total of 20 (15%) developed CI-AKI . Patients with CI-AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p < 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p < 0.001). There were no significant changes between NGAL 0 & 24 hours within the 2 groups( figure 1). According to the ROC curve analysis (figure 2), the optimal NGAL 0 level for CI-AKI prediction was >125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p < 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0<125 ng/mL was 94%. Conclusions Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of CI-AKI.NGAL 0 vs 24 according to CI-AKINGAL AUC

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1β) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1β, glucose, and CEA, and serum for Ngal and IL-1β. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1β and serum Ngal made no diagnostic contribution.

Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

Can neutrophil gelatinase-associated lipocalin be a novel and efficient marker to predict the clinical course of acute pancreatitis?

This study aimed to determine the value of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels to predict the severity of the disease and to identify its correlation with White Blood Cell (WBC), C-reactive protein (CRP), and high-sensitivity C-reactive protein (hs-CRP) levels in acute pancreatitis (AP). The study sample included 86 AP-diagnosed patients in the study group and 77 age- and gender-matched healthy volunteers with no comorbidity in the control group. The WBC, CRP, hs-CRP, and NGAL levels were examined at the time and 24 hours after diagnosis. Between the control group and the study group, a significant difference with and without necrosis in terms of NGAL averages (p=0.003) at the time of admission was observed. The mean level of the 24th-hour NGAL in the study group with necrosis (132.7±11.7 ng/ml) was found to be higher than the mean of the 24th-hour NGAL (117.5±22.6 ng/ml) in the study group without necrosis (p=0.032). Additionally, a significant difference was observed between the control group and the study group with and without necrosis in terms of CRP averages evaluated at admission. When the correlation of NGAL levels with WBC, CRP, and hs-CRP levels at the admission (r=0.224, p=0.038) and at the 24th h (r=0.389, p<0.001) are evaluated, weak correlations between NGAL and WBC levels were identified, but no correlation between NGAL and CRP and hs-CRP levels were observed. The usability of serum NGAL levels to predict the development of necrotizing pancreatitis in the early period was evaluated. Serum NGAL levels were found to be higher in the study group than in the control group, but there was no statistically significant difference between the mean values of 0th and 24th h NGAL values in any of the groups with/without pancreatic necrosis and the total study group was observed. More research is needed on the subject, with larger sampling sizes.

Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Dialysis-Related Peritonitis: Correlation with White Blood Cells over Time and a Possible Role as the Outcome Predictor

Introduction: The present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome. Methods: Twenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test). Results: We found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p > 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups. Conclusion: This study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.

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.

Early Diagnostic Value of KIM-1, NGAL, and NLR in Acute Kidney Injury Caused by Diquat Poisoning

Background. The kidney is the main excretory organ after diquat absorption. Acute kidney injury (AKI) is a common complication in diquat poisoning patients. Objectives. To identify the value of combined detection of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and neutrophil-lymphocyte ratio (NLR) in the early diagnosis of diquat-induced AKI. Materials and Methods. The retrospective cohort study included 42 diquat poisoning patients. Results. Forty-two patients with diquat poisoning were included, of which 20 had fulminant poisoning (47.6%). At admission (0 h), levels of KIM-1, NGAL, NLR, and acute physiology and chronic health evaluation (APACHE) II scores in the fulminant poisoning group were higher than that of the moderate to severe poisoning group ( P &lt; 0.05), and they were all higher than in the control group ( P &lt; 0.05), while blood urea nitrogen (BUN) and uric acid (UA) levels did not significantly differ across the three groups ( P &gt; 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores of patients in the fulminant poisoning group were higher than those in the moderate to severe poisoning group ( P &lt; 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( P &lt; 0.05). Among 42 patients with diquat poisoning, 28 had AKI (66.7%). At 0 h, the AKI group had higher levels of KIM-1, NGAL, NLR, and APACHE II scores than in the non-AKI (NAKI) group ( P &lt; 0.05), while there was no significant difference in BUN and UA levels between the two groups ( P &gt; 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores in the AKI group were higher than those in the NAKI group ( P &lt; 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( P &lt; 0.05). KIM-1, NGAL, and NLR are independent risk markers for AKI in diquat poisoning patients. At admission (0 h), the combined application of KIM-1, NGAL, and NLR’s sensitivity, specificity, and area under the curve (AUC) for predicting AKI in diquat poisoning patients was 0.893, 0.859, and 0.903, respectively. Conclusions. KIM-1, NGAL, and NLR can be employed as early diagnostic indicators for the clinical prediction of AKI in diquat poisoning patients. Our findings may help clinicians reduce the occurrence of AKI.

The value of plasma NGAL and NT-proBNP in the diagnosis of type 1 cardiorenal syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background The presence of acute kidney injury in the setting of acute heart failure (AHF) is common occurrence and was termed type 1 cardiorenal syndrome (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. NT-proBNP has a role in the diagnosis of acute heart failure. Does the combination of NGAL and NT-proBNP increase diagnostic value of CRS1? This study was aimed to evaluate the diagnostic value of plasma NGAL and NT-proBNP in diagnosis of CRS1. Methods there were 139 patients with AHF in the department of Cardiovascular resuscitation and Interventional cardiology Ho Chi Minh City Vietnam 115 People Hospital from September 2018 to March 2019. This was a prospective cohort study. Results the optimal cut-off plasma NGAL to diagnosing CRS1 was 353.23 ng/ml, Area Under Curve (AUC) 0.732 (95% CI 0.65-0.80, p &amp;lt; 0.001), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, negative predictive value 84%. The optimal cut-off NT-proBNP to diagnosing CRS1 was 17681 pg/ml, AUC 0.710 (95% CI 0.627-0.784, p &amp;lt; 0.001), sensitivity 54.2%, specificity 80.2%, positive predictive value 59.1%, negative predictive value 76.8%. Combination of plasma NGAL and NT-proBNP in diagnosing CRS1 with AUC 0.756 (95% CI 0.676-0.825, p &amp;lt; 0.001), sensitivity 77.1%, specificity 69.2%, positive predictive value 56.9%, negative predictive value 85.1%. Conclusions Combination of plasma NGAL and NT-proBNP in the diagnosis of type 1 cardiorenal syndrome with higher sensivity than each biomarker.

The value of plasma NGAL and Cystatin C in the diagnosis of type 1 cardiorenal syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background The presence of acute kidney injury in the setting of acute heart failure (AHF) is common occurrence and was termed type 1 cardiorenal syndrome (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. Cystatin C has a role in the diagnosis renal dysfunction. Does the combination of NGAL and Cystatin C increase diagnostic value of CRS1? This study was aimed to evaluate the diagnostic value of plasma NGAL and Cystatin C in diagnosis of CRS1. Methods there were 139 patients with AHF in the department of Cardiovascular resuscitation and Interventional cardiology Ho Chi Minh City Vietnam 115 People Hospital from September 2018 to March 2019. This was a prospective cohort study. Results the optimal cut-off plasma NGAL to diagnosing CRS1 was 353.23 ng/ml, Area Under Curve (AUC) 0.732 (95% CI 0.65-0.80, p &amp;lt; 0.001), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, negative predictive value 84%. The optimal cut-off Cystatin C to diagnosing CRS1 was 1.81 mg/l, AUC 0.787 (95% CI 0.71-0.852, p &amp;lt; 0.001), sensitivity 75%, specificity 83.5%, positive predictive value 70.6%, negative predictive value 86.4%. Combination of plasma NGAL and Cystatin C in diagnosing CRS1 with AUC 0.787 (95% CI 0.71-0.852, p &amp;lt; 0.001), sensitivity 72.9%, specificity 86.8%, positive predictive value 74.5%, negative predictive value 85.9%. Conclusions Combination of plasma NGAL and Cystatin C in the diagnosis of type 1 cardiorenal syndrome with higher specificity than each biomarker.

NGAL (Neutrophil Gelatinase-Associated Lipocalin) as an early biomarker of nephropathy in patients with type 2 diabetes

ABSTRACT Background and aim Diabetic nephropathy (DN) is a major microvascular diabetic complication representing the key leading reason for end-stage renal disease (ESRD). The current work aimed to evaluate the value of urinary and serum NGAL (neutrophil gelatinase-associating lipocalin), as an early biomarker of DN in subjects with type-2 diabetes mellitus (T2DM). Methods The study included 300 adult subjects with T2DM subdivided into 3 groups: Group A: 100 subjects with normoalbuminuria. Group B: 100 subjects with moderately increased albuminuria. Group C: 100 subjects with severely increased albuminuria. Results Serum NGAL and urinary NGAL were significantly elevated in T2DMsubjects with albuminuria than in normoalbuminuric T2DMsubjects (p < 0.001). Serum NGAL and urinary NGAL were positively associated with albumin/creatinine Ratio, (p < 0.001). ROC curve analysis was done to discriminate among moderately/severely increased albuminuria from normoalbuminuria showed a cutoff point ≤ 10.76 for serum NGAL with AUC 0.785 (p value < 0.001) and a cutoff point ≤ 15.811 with AUC 0.687 for urinary NGAL(p < 0.001). Conclusion NGAL can be utilized as a biomarker for the early diagnosis of DN. Both urinary NGAL and serum NGAL may predict albuminuria and can be utilized as a noninvasive tool for diagnosing, grading, and progressions of DN.

The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study

BackgroundPercutaneous coronary intervention (PCI) is one of the most performed well-succeeded therapeutic procedures worldwide, reducing symptoms and improving quality of life. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) produced early after an ischemic renal insult. Osmotic diuresis and the vasoconstriction of the afferent arteriole promoted by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) generate a concern regarding the possibility of dehydration and consequent AKI. There is no consensus on the maintenance or discontinuation of SGTL2i in patients who will undergo PCI. This study aimed to evaluate the safety of empagliflozin in diabetic patients submitted to elective PCI regarding kidney function.MethodsSAFE-PCI trial is a prospective, open-label, randomized (1:1), single-center pilot study and a follow-up of 30 days. The SGLT2i empagliflozin 25 mg daily was initiated at least 15 days before PCI in the intervention group and maintained until the end of the follow-up period. Serum NGAL was collected 6 h after PCI and creatinine before PCI, 24 h, and 48 h after the procedure. As per protocol, both groups received optimal medical treatment and standard protocol of nephroprotection.ResultsA total of 42 patients were randomized (22 patients in the iSGLT-2 group and 20 patients in the control group). There was no difference between-group baseline data. The primary outcome (NGAL and creatinine values post PCI) did not differ in both groups: the mean NGAL value was 199 ng/dL in the empagliflozin group and 150 ng/dL in the control group (p = 0.249). Although there was an initial increase in creatinine in the SGLT-2i group compared to the control group between baseline creatinine and pre-PCI and 24 h post-PCI creatinine, no difference was detected in creatinine 48 h post-PCI (p = 0.065). The incidence of CI-AKI, determined by KDIGO criteria, in the iSGLT2-group was 13.6% and 10.0% in the control group without statistical difference.ConclusionThe present study showed that the use of empagliflozin is safe regarding kidney function during elective PCI in patients with T2D when compared with no use of SGLT2i.Trial registration Our clinical study is registered on ClinicalTrials.gov with the following number: NCT05037695.

#4479 KIM-1, IL-18 AND NGAL IN MACHINE LEARNING PREDICTION OF KIDNEY INJURY AMONG CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract Background and Aims Children undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) are particularly vulnerable to acute kidney injury (AKI), especially in the early post-transplantation period. The major risk factors of AKI development are aggressive immunosuppression and infectious complications. In the meantime, malnutrition and hypermetabolic state of the patient, together with the routine intensive hydration during first 3 weeks after HSCT and subsequent forced diuresis, alter the serum creatinine concentration, modifying the estimated glomerular filtration rate (eGFR) value too. Therefore, the risk of underrating serum creatinine and overrating eGFR values is high, making the assessment of the degree of kidney damage during the first month after HSCT a challenge. Therefore, markers of tubular dysfunction and damage, like kidney injury molecule (KIM)-1, neutrophil gelatinase-associated lipocalin (NGAL) or interleukin (IL)-18, may be of added value while assessing renal function and analyzing the risk of AKI in this population. The aim of study was to assess the serum concentrations of damage biomarkers (KIM-1, NGAL, IL-18) in children undergoing alloHSCT, in relation to another surrogate marker of renal dysfunction, hyperfiltration. Another aim was to analyze the potential value of KIM-1, NGAL, and IL-18 as predictors of kidney damage in children after alloHSCT, with the use of artificial intelligence tools. Method The study group contained 22 children undergoing alloHSCT, followed up for 4 weeks after transplantation. Serum concentrations of KIM-1, NGAL, and IL-18 were assessed by ELISA in fixed time points (before HSCT, 1 day after HSCT, 1, 2 3, 4 weeks after transplantation). eGFR values (counted based on Schwartz formula) and the rate of hyperfiltration (eGFR &amp;gt; 140ml/min/1.73sq.m.) were evaluated at the beginning (before HSCT) and at the end (4 weeks after HSCT) of observation, when neither hydration nor diuretics were used. Statistical analysis was performed with the use of package Statistica, the comparisons between paired data were evaluated by using nonparametric tests (Friedman, Wilcoxon). Additionally, the patients within the database were randomly divided into two groups. The training group allowed to build a Random Forest Classifier (RFC) with the highest possible predictive power, while the testing group allowed to assess the effectiveness of prediction on new data and the clinical utility. Moreover, the contribution of individual variables was evaluated by GINI importance. Results KIM-1, NGAL, and IL-18 serum concentrations increased systematically until the 3rd week after HSCT, with statistically significant differences between subsequent observation points, then remained elevated until the 4th week after HSCT. Median eGFR values before transplantation and 4 weeks after HSCT were comparable, although the rate of patients with hyperfiltration increased. The RFC model built on the basis of 3 input variables, KIM-1, NGAL, and IL-18 concentrations in serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration 4 weeks after the procedure. RF Classifier achieved AUROC of 0.8333, accuracy of 80.00%, positive predictive value of 0.8667, and sensitivity of 0.8000. The contribution of KIM-1, IL-18 and NGAL to the prediction in this model was comparable (33.73%, 32.77%, and 33.5%, respectively). Conclusion KIM-1, NGAL, and IL-18 are useful in assessing acute tubular damage in children after HSCT. Their values before HSCT may also serve as markers of incipient renal dysfunction 4 weeks after alloHSCT. The developed model seems a clinically useful tool to target patients who are at risk of kidney injury after HSCT. The Random Forest Classifier seems a promising tool for such analysis, that should be tested on a larger group of patients.

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.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Patients with ST-Elevation Myocardial Infarction and Its Association with Acute Kidney Injury and Mortality.

Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker related to acute kidney injury (AKI). Including 1892 consecutive patients with ST-elevation myocardial infarction (STEMI), in which NGAL was measured in 1624 (86%) on admission and in a consecutive subgroup at 6-12 h (n = 163) and 12-24 h (n = 222) after admission, this study aimed to evaluate the prognostic value of NGAL in predicting AKI and mortality. Patients were stratified based on whether their admission NGAL plasma concentration was greater than or equal to/less than the median. The primary endpoint was a composite of the first occurrence of AKI or all-cause death within 30 days. AKI was classified by the maximal plasma creatinine increase from baseline during index admission as KDIGO1 (<200% increase) or KDIGO23 (≥200% increase) according to the Kidney Disease Improving Global Outcomes (KDIGO) system. Admission NGAL > the median was independently associated with a higher risk of severe AKI (KDIGO2-3) and 30-day all-cause mortality when adjusted for age, admission systolic blood pressure and high-sensitivity C-reactive protein, left-ventricular ejection fraction, known kidney dysfunction, and cardiogenic shock with an odds ratio (95% confidence interval) of 2.26 (1.18-4.51), p = 0.014. Finally, we observed increasing predictive values in a subgroup during the first day of hospitalization suggesting that assessment of NGAL should be delayed for optimal prognostic purposes.