Neutrophil Gelatinase-associated Lipocalin Measurement Research Articles

THE ROLE OF CYTOKINE PROFILE IN THE DEVELOPMENT OF ACUTE RENAL PATHOLOGY IN CHILDREN WITH COVID -19

Objective: This study aimed to investigate the impact of Covid-19 on the development of tubulointerstitial kidney damage in children, focusing on cytokine profiles, kidney function, and the role of neutrophil gelatinase-associated lipocalin (NGAL) as a marker for kidney injury. Methods: A cohort of 132 children who experienced tubulointerstitial kidney damage post-Covid-19 was studied. The patients were divided into two groups: one with acute pyelonephritis (AP) and the other with acute tubulointerstitial nephritis (ATIN). Diagnostic methods included blood and urine analysis, renal ultrasound, cytokine profiling (IL-6, IL-4, TNF-α, γ-INF), and NGAL measurement. Results: The study found significantly elevated NGAL levels in the urine of children with AP and Covid-19 compared to healthy controls (110.74±1.27 vs. 65.66±0.64 ng/mg creatinine; p<0.001). Cytokine analysis revealed substantial increases in IL-6, TNF-α, and γ-INF, particularly in children with Covid-19-related kidney damage, suggesting a severe inflammatory response contributing to kidney dysfunction. Novelty: This research highlights the crucial role of cytokines in kidney injury following Covid-19 in children and emphasizes NGAL as a reliable biomarker for early detection of renal damage, offering new insights for treatment and prognosis.

Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study. Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL-0) and 24 h after (NGAL-24). Similar analysis of C-reactive protein (CRP) was performed for additional comparison. Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL-0 (164 vs. 95 ng/mL; p < 0.001) and NGAL-24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL-0 and NGAL-24 were similar within the AKI and non-AKI groups. Using ROC curve analysis, NGAL-0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80-0.96), compared with NGAL-24 (0.783, 95% CI 0.74-0.85), CRP-0 (0.701, 95% CI 0.58-0.83), and CRP-24 (0.781, 95% CI 0.66-0.90). The optimal NGAL-0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value. Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI.

#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.

#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 &amp;lt; 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p &amp;lt; 0.001). There were no significant changes between NGAL 0 &amp; 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 &amp;gt;125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p &amp;lt; 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0&amp;lt;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.

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

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 &amp;lt; 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p &amp;lt; 0.001). There were no significant changes between NGAL 0 &amp; 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 &amp;gt;125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p &amp;lt; 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0&amp;lt;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

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

Protective effects and mechanisms of dapagliflozin on renal ischemia/reperfusion injury

BackgroundRenal diseases have a significant negative impact on human health and the quality of life. Renal ischemia/reperfusion (I/R) injury is considered as one of the leading causes of renal dysfunction and tissue damage. Oxidative stress and inflammation are responsible for cellular apoptosis playing critical roles in renal I/R injury. Recent studies suggested that dapagliflozin—a medication used to treat Type 2 Diabetes—may exert protective effects on I/R injury in kidneys by alleviating oxidative stress and inflammation. Our study evaluated the protective effects of dapagliflozinon in renal I/R injury. MethodsA group of 32 male Sprague-Dawley rats were divided into four groups: 1) control group without any manipulation; 2) sham-operated control group with surgery but without I/R injury; 3) experimental group with 30-min I/R injury; and 4) therapeutic group with 30-min IR injury and dapagliflozin therapy. The fourth therapeutic group received 1 mg/kg dapagliflozin delivered once daily by oral gavage. All rats were evaluated by measurements of neutrophil gelatinase-associated lipocalin (NGAL), creatinine kinase (CR), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), myoglobin (MYO), creatinine kinase (CK), lactate dehydrogenase (LDH) LD, GSH, superoxide dismutase (SOD), MDA, interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a and glutathione peroxidase (GSH-Px) levels. TUNEL and flow cytometry assays evaluated apoptosis. ResultsOverall, the 30-min exposure to I/R injury significantly elevated levels of NGAL, CR, BUN, CK, LDH, KIM-1, and MYO (all p < 0.05). Inflammatory cytokine levels (IL-6 and TNF-a) were also increased after I/R injury (p > 0.05). At the same time, I/R injury decreased levels of SOD and GSH-Px (p > 0.05). In contrast, administration of dapagliflozin following I/R injury reduced renal damage, enhanced antioxidant capacity, and suppressed inflammatory responses (all p > 0.05), thus improving renal function, while reducing oxidative stress status and inflammatory responses. Further investigations revealed that dapagliflozin exerted its protective effects on renal tissues by activating the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, inhibiting cellular apoptosis, and promoting proliferation and autophagy through bone morphogenetic protein 4 (BMP4). ConclusionThese findings documented that dapagliflozin protected kidneys from I/R injury suggesting its therapeutic potential.

Serum neutrophil gelatinase-associated lipocalin as promising diagnostic marker and a predictor of activity of ulcerative colitis patients: single center study

Objective The study aimed to detect the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) in ulcerative colitis (UC) patients, and to evaluate the relation between its value and the clinical activity of the disease. Background Inflammatory bowel disease including UC is chronic inflammatory gastrointestinal disease characterized by remissions and exacerbations and needs invasive diagnosis. Serum NGAL is type of protein its expression is increased in inflamed intestine, and released from activated neutrophils. Patients and methods The study was performed on 75 patients with UC diagnosed by laboratory investigations including erythrocyte sedimentation rate, C-reactive protein, and complete blood count, lower endoscopy, histopathological examination, and activity according to Mayo score was recorded. Also 30 healthy control age sex matched, both groups subjected to measurement of serum NGAL. Results There was highly significant elevation of serum NGAL in UC patients compared with healthy control with P value less than 0.001, moreover serum NGAL was positively correlated with clinical activity of the disease as recorded by Mayo score. The study show cut off value of NGAL more than 74 ng/ml with sensitivity 96% and specificity 66.7%. Conclusion Serum NGAL can be used as noninvasive diagnostic marker of UC and corresponds to clinical and endoscopic activity of the disease.

Measurement of Neutrophil Gelatinase-Associated Lipocalin (Ngal) Following Neuroradiological Procedure/s in Patients with Aneurysmal Subarachnoid Hemorrhage: A Preliminary Study.

Radiocontrast administration during interventional neuroradiology (INR) procedures for aneurysmal subarachnoid haemorrhage (aSAH) can add to renal insult. Serum creatinine (sCr) is a conventional marker of acute kidney injury (AKI). Serum neutrophil gelatinase-associated lipocalin (sNGAL) is a novel marker which is increasingly used to predict renal injury in susceptible patients. The primary aim of this study was to evaluate correlation between serum neutrophil gelatinase-associated lipocalin (NGAL) and sCr in aSAH patients undergoing therapeutic or diagnostic INR procedures. The secondary aim was to find the incidence of contrast-induced AKI and hemodynamic complications during the study period. All consenting aSAH patients (18-60 years, Modified Hunt and Hess grade 1-4) posted for INR procedures during the study time were included. Patients with history of chronic renal disease, recent contrast exposure, or renal insufficiency were excluded. Blood samples for sCr and sNGAL were obtained preprocedure and then at 1, 6, 24, and 48 h after contrast administration. Hourly urine output was noted. AKI was defined by KDIGO guidelines. Repeated measurement analysis of variance, Posthoc Bonferroni test and Pearson correlation coefficient test. Fifty patients, mean age 47.34 ± 9.31 years, were enrolled for the study. Majority (48; 96%) were Hunt and Hess (H and H) grade I-III. The mean volume of contrast administered was 123.2 ± 53.08 mL. The mean sNGAL and sCr values at pre-op, 1, 6, 24, and 48 h were 124.99 ± 64.58, 148.40 ± 77.90, 147.33 ± 76.00, 125.49 ± 64.44, and 116.38 ± 61.79 ng/mL and 0.629 ± 0.23, 0.624 ± 0.22, 0.612 ± 0.21, 0.632 ± 0.19, and 0.577 ± 0.22 mg/dL, respectively. There was a correlation in sCr and sNGAL value (P < 0.001) at all study time points. However, no specific pattern was seen. No patient developed any AKI or hemodynamic complications in first 48 h. There is a correlation between serum NGAL and sCr at individual time points. NGAL may represent a sensitive early biomarker of renal impairment after INR Procedures. There was no incidence of AKI after contrast administration in aSAH patients without predisposing renal risk factors.

Incidences of and risk factors for clinical and subclinical contrast-associated acute kidney injury in patients who underwent neuroendovascular surgery.

Contrast-associated acute kidney injury (CA-AKI) can develop after intravascular administration of iodinated contrast media. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI that helps to detect subclinical CA-AKI. We investigated the incidence of and risk factors for clinical and subclinical CA-AKI in patients who underwent neuroendovascular surgery. We retrospectively investigated 228 patients who underwent neuroendovascular surgery in 2020. Changes in serum creatinine and urine output were used to detect clinical CA-AKI. Urine NGAL concentration was used to detect subclinical CA-AKI in 67 out of 228 patients. In 228 patients, serum creatinine, hemoglobin, hematocrit, total protein, and blood urea nitrogen (BUN) decreased significantly (p < 0.001) after surgery. However, serum creatinine decreased less significantly (p < 0.05) than hemoglobin, hematocrit, total protein, and BUN on postoperative Day 3. Two patients out of 228 developed clinical CA-AKI, and seven patients out of 67 with urine NGAL measurements developed subclinical CA-AKI. Multivariate regression analysis revealed that diabetes mellitus and carotid artery stenosis were significantly (p < 0.05) associated with the development of clinical and/or subclinical CA-AKI. There was a large difference between the incidences of clinical CA-AKI (0.88%) and subclinical CA-AKI (10.4%). The difference might have primarily resulted from the different sensitivities between serum creatinine and urine NGAL and possibly from underestimation of the incidence of clinical AKI due to a postoperative decrease in serum creatinine caused by hemodilution. In addition to diabetes mellitus, carotid artery stenosis could also be a risk factor for CA-AKI.

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.

Relation of Baseline Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Contrast-Induced Nephropathy following Percutaneous Coronary Intervention among Chronic Kidney Disease Patients.

Background: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). Methods: Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. Results: Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96–40.3; p = 0.01). Conclusion: Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.

Value of point-of-care neutrophil gelatinase associated lipocalin in early diagnosis of acute kidney injury in patients with left ventricular systolic dysfunction after coronary angiography

Background: Increased neutrophil gelatinase-associated lipocalin (NGAL) levels are associated with toxic or ischemic renal injury. Objective: This study aimed to assess the usefulness of serial NGAL measurements with a point-of-care assay in patients with left ventricular systolic dysfunction (LVSD) for earlier detection of contrast-induced nephropathy (CIN). Materials and methods: A total of 84 patients with LVSD patients referred for coronary angiography were consecutively enrolled in the study. The study population was divided into two groups as the CIN and the non-CIN groups according to the CIN's determination. The serum creatinine levels were calculated 24 h before the procedure and at the 48th and 72nd h after the cardiac catheterization. The plasma NGAL concentration was measured before and at 4 and 24 h after the cardiac catheterization. Results: Baseline and serial NGAL levels were significantly higher in patients with CIN compared to the patients without CIN. NGAL 24th h levels after the index procedure were found to be an independent and significant predictor of CIN in multivariate analysis. Conclusions: Serial point-of-care NGAL measurements might help earlier detection of CIN in patients with heart failure after coronary angiography.

Neutrophil Gelatinase-Associated Lipocalin Contributes to Increased Risk of Cardiovascular Death After Acute Coronary Syndrome.

BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) has been suggested to reflect early renal dysfunction. We investigated the predictive significance of serum NGAL in predicting cardiovascular (CV) death in an old-age population with coronary heart disease (CHD).MethodsIn total, 633 CHD patients with a stable clinical condition were enrolled. The measurements of serum NGAL and other laboratory indices were performed within 24 hours after admission. Adjusted analysis was used to assess relationships between serum NGAL and CV death during the 10-year follow-up period.ResultsMultivariate logistic regression analysis demonstrated that elevated NGAL levels were related to a higher prevalence of CV disease history [quartile 4, 2.41 (1.60–4.59), P-trend <0.001]. The Kaplan–Meier curve indicated that patients with high NGAL levels tended to have a higher rate of CV death than patients with low NGAL levels. A multivariate Cox model suggested that increased levels of NGAL were independently linked with elevated risk of CV death (HR=2.62, 95% CI 1.51–4.96, P<0.001) during the 10-year follow-up period, after adjusting for related confounding factors using sensitivity analysis. Furthermore, the receiver operating characteristics (ROC) curve demonstrated that serum NGAL (AUC=0.917, 95% CI 0.895–0.940, P<0.001) had an ideal predictive value in predicting CV death.ConclusionSerum levels of NGAL were elevated in patients with CHD and may be a new parameter that could independently predict CV death in these patients, which may strengthen its potential application in clinical practice.

Analytical validation and reference intervals for a commercial multiplex assay to measure five novel biomarkers for acute kidney injury in canine urine

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration.The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/− 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20–22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).

Urine neutrophil gelatinase-associated lipocalin (NGAL) measurement is not predictive for ureteral patency in pediatric patients following pyeloplasty: a pilot study

Objective: To evaluate the benefit of urine neutrophil gelatinase-associated lipocalin (NGAL) measurement to predict the ureteral patency in pediatric patients undergoing pyeloplasty. Materials and Methods: Ureteropelvic junction obstruction patients who underwent unilateral dismembered pyeloplasty had urine NGAL measurements taken intraoperatively during pyeloplasty and postoperatively at six months following surgery. All patients were evaluated preoperatively and postoperatively with renal scans. Pairwise comparisons and correlation analyses were performed to determine the dynamics and benefits of urine NGAL measurement. Results: Thirteen patients were included in this pilot study with a mean age of 3.2 years at surgery. Mean intraoperative bladder urine level was 4.43 ng/mL, and median intraoperative renal pelvic urine NGAL level was 3.70 ng/mL. There was no significant difference between these two levels (p-value = 0.76). Six months after pyeloplasty, 9/13 patients demonstrated significant reduction in the bladder urine NGAL level (at least 50% reduction), and 5/13 patients showed ureteral patency based on postoperative renal scan (more than 5% improvement in differential renal function or the conversion of diuretic half time. However, the finding of significant reduction of urine NGAL level did not correlate with ureteral patency (r = -0.50, p-value = 0.08). Conclusion: Although bladder urine NGAL level reduces in most pediatric patients following pyeloplasty, this decline is not reflective of the finding of ureteral patency from renal scanning. The benefits of urine NGAL measurement in this context remain unclear and require further large-scale investigation.

Renal effect of severe hypoxia evaluated By NGAL measurements: An in vivo and in vitro study.

To investigate possible renal damage in healthy men exposed to extreme hypobaric hypoxia, using urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration as biomarker. The value of NGAL as a biomarker of proximal tubular cell damage under hypoxic conditions was also tested in vitro experiments. NGAL was assayed in a cohort of air cadets (n = 16) exposed to hypobaric hypoxia in a hypobaric chamber during their training program. In all subjects, urine creatinine (Cr) and urinary NGAL levels were measured immediately before, 3, and 24 h after hypobaric environment exposure. Three in vitro experiments using proximal tubular cell cultures were also performed to measure NGAL gene expression, NGAL secretion in the culture medium and to evaluate apoptosis under two cycles of hypoxia and reoxygenation. In the in vivo study, geometric means of urinary NGAL/Cr ratio measured 24 h after hypobaric hypoxia in the hypobaric chamber were significantly lower than baseline values (13.4 vs 25.9 ng/mg, p = 0.01). In cell cultures, hypoxia down-regulated NGAL gene expression without significantly changing NGAL secretion in the culture medium. Hypoxia significantly increased the percentage of apoptotic/necrotic cells, especially after the second hypoxia-reoxygenation cycle. Exposure to hypobaric-hypoxic environments does not cause significant and irreversible renal tubular injury in vivo and in vitro, except than in a late stage. The hypoxic insult does not seem to be mirrored by an increase of urinary NGAL in healthy men nor of NGAL gene expression in HK-2 cell culture or secretion in the culture medium in the in vitro conditions reported in the present study.

POS-072 PRACTICAL EXPERIENCE WITH THE IMPLEMENTATION OF NGAL FOR AKI DIAGNOSIS IN A CLINICAL SETTING

Kidney injury biomarkers for AKI have been shown to detect AKI earlier, predict progression and better discriminate etiology compared to serum creatinine. These biomarkers have been studied in various clinical trials, but their implementation and prediction capacity in standard clinical settings have rarely been reported. We describe our initial clinical experience during the implementation of the Neutrophil gelatinase-associated lipocalin (NGAL) in our academic medical centre. We prospectively audited the initial implementation and use of urine and plasma NGAL (uNGAL, pNGAL) as diagnostic biomarkers in hospitalised patients with newly diagnosed AKI. This novel biomarker was ordered only by the Nephrology Consult service. Questionnaires for initial evaluation of the suspected etiology and risk of progression were completed by the consulting renal team before and one day after usual diagnostic workup. NGAL results were available for the second follow-up assessment. An NGAL level of 150 ng/mL was used by the SVUH Clinical Biochemistry Laboratory as the cut-off value to discriminate the presence of tubular damage (range 25-3000 ng/mL). An attending nephrologist, not involved in the care of these patients, independently conducted a retrospective review using medical records, to determine the most likely etiology of AKI, and whether or not clinical progression occurred following initial renal consultation. Descriptive statistics and Mann-Whitney U tests were used for analyses. This audit was pre-approved by the SVUH Clinical Audit Committee. Between May and October 2020, 47 NGAL samples were measured (uNGAL, n=23; pNGAL, n=24) in 26 AKI patients, with a median age of 66.5 (IQR 55.3-81.0). Chronic kidney disease was present in 12 (46%) patients. Stage 1, 2 and 3 AKI occurred in 6 (23%), 11 (42%), and 9 (35%) patients, respectively. The median delay between admission and NGAL measurement was 4 (IQR 0-20) days. The creatinine level at diagnosis was similar for pre-renal AKI (median 224 (IQR 157-340) umol/L) and intra-renal AKI (median 247 (IQR 193-487) umol/L). Urine NGAL was 41 (IQR 29-280) ng/mL in the pre-renal group, compared to 1308 (IQR 175-1361) ng/mL for intra-renal AKI (p=0.08), while pNGAL were 251 (IQR 99-340) ng/mL and 420 (IQR 255-865) ng/mL (p=0.19), respectively. NGAL levels were higher in the subgroup of ischemic ATN (uNGAL: 1332 (IQR 888-1365) ng/mL; pNGAL: 495 (IQR 384-889) ng/mL) compared to toxic ATN (uNGAL: 178 (IQR 105-1389) ng/mL; pNGAL 208 (IQR 139-751) ng/mL). According to adjudication, the initial clinical impression of AKI etiology was incorrect in 3 patients (12%), while the initial prediction of progression vs. non-progression was incorrect in 8 patients (31%). In those 8 patients, NGAL values correctly predicted progression in 7 of them. We reported the early use of both uNGAL and pNGAL in clinical practice on the Nephrology consultation service in an academic medical centre. Based on our experience, we consider that NGAL, especially uNGAL can be an interesting tool for differential diagnosis and to predict AKI progression. The diagnostic accuracy of NGAL tests for these purposes may be improved by using a higher cut-off level to determine the etiology and prognosis of new AKI cases. Additional integration of NGAL tests into clinical algorithms for AKI management and follow-up audits are required.