Median Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

L-FABP and NGAL are novel biomarkers for detection of abdominal injury and hemorrhagic shock

IntroductionDelayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries. Patients and MethodsTraumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury (“Abd”) and 10 patients had an abdominal injury with hemorrhagic shock (“HS Abd”). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 (“noAbd”) were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. ResultsAll patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in “HS Abd” group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to “noAbd” group (36.4 ng/ml [IQR=14.8–88.5]), and to “Abd” group (41.4 ng/ml [IQR=18.0–235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group “Abd” were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to “noAbd” (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in “HS Abd” group (115.9 ng/ml [IQR=90.6–163.8]) compared to “noAbd” group (58.5 ng/ml [IQR=41.0–89.6],p<0.001) and “Abd” group (70.5 ng/ml [IQR=53.3–115.5], p<0.05). The group “Abd” showed significant higher median NGAL levels compared to “noAbd”, p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. Conclusion:L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.

Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression.

BackgroundAcute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population.MethodsWe conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay. ResultsA total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81–201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97–267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714–0.853). ConclusionsNGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.

Serum Neutrophil Gelatinase-Associated Lipocalin Independently Predicts for Renal Response in Myeloma Patients with Severe Renal Impairment

Introduction: Severe renal impairment (RI) is a common complication of multiple myeloma (MM). Effective anti-MM therapy and supportive care can restore renal function in several patients, but we lack biomarkers that could predict renal outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the earliest and most robust markers of acute kidney injury while serum Cystatin C (CysC) reflects renal function more accurately than creatinine and correlates with both tumor burden and renal function in MM. GDF-15 is secreted by bone marrow stromal cells and high serum levels indicate a poor treatment prognosis and a high risk of progression to dialysis in AL amyloidosis. Our aim was to evaluate serum NGAL, CysC, and GDF-15 in MM patients with severe RI defined as eGFR&lt;30 ml/min/1.73m2, by CKD-EPI formula, including those on dialysis, as biomarkers for prediction of renal responses. Patients &amp; Methods: MM patients who presented with myeloma-related severe RI in the Department of Clinical Therapeutics (Athens, Greece) were included in this study. NGAL, CysC and GDF-15 were measured in the same frozen serum sample collected before the administration of any therapy. Serum NGAL was measured using ELISA (BioPorto Diagnostics A/S, Gentofte, Denmark), while CysC was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). GDF-15 was measured by a novel immunoassay, the Elecsys GDF-15 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), which is based on the sandwich immunoassay principle using biotin-streptavidin technology. Patients on dialysis received dialysis with regular membranes. IMWG renal response criteria were used. Results: In total, 101 newly diagnosed MM patients with severe RI were included in this analysis. Median creatinine was 4.6 mg/dl (range 2-&gt;10 mg/dl), median eGFR (ml/min/1.73 m2) was 11.3 (1.3-29.8) and dialysis was required in 35 (35%) patients. The median age was 71 years; median involved FLC was 4740 mg/L; hypercalcemia was found in 24%, LDH ≥ULN in 44% and high-risk cytogenetics in 25% of patients, while 98% of patients were classified as having ISS-3 and 49% as having R-ISS-3 disease stage. Treatment was bortezomib-based in all patients (in 21% VD and in 79% a triplet: VCD or VTD). Median NGAL levels were 182.3 ng/mL (range 20-550 ng/ml) and of CysC were 3.3 mg/L (0.9-8 mg/L); there was a strong correlation between NGAL and CysC levels (R2=0.653, p&lt;0.001). There was also a strong correlation of both CysC and NGAL with eGFR (for CysC: R2=0.615, p&lt;0.001 and for NGAL: R2=0.464, p&lt;0.001). Both NGAL and CysC levels were higher in patients requiring dialysis vs those not in dialysis (median NGAL: 308 vs 166 ng/mL, p&lt;0.002 and median CysC: 4.99 vs 2.83 mg/L, p=0.008). No significant correlations were observed with GDF-15 and the parameters tested. Renal response (Rrenal) was achieved in 63% of patients, including 45% with major Rrenal. Importantly, 40% of patients who required dialysis became dialysis independent. Median time to Rrenal was one month and median time to dialysis independence was two months. Lower levels of NGAL (p=0.0003) and CysC (p=0.03) were associated with higher probability of major Rrenal among patients with severe RI. Baseline eGFR, levels of sFLC and GDF-15 did not correlate with major Rrenal. None of these markers was associated with probability of dialysis independence among patients who required dialysis. Based on ROC analysis, in patients with severe RI (but not on dialysis), NGAL &lt;138 ng/ml was strongly associated with major Rrenal (80% vs 20% at 3 months, p&lt;0.001; Figure). Regarding CysC, levels &lt;2.9 mg/L were associated with higher probability and shorter time to major Rrenal (p=0.012). In multivariate analysis performed in patients not on dialysis, that included age, NGAL, CysC and eGFR, only NGAL &lt;138ng/ml remained a significant prognostic factor associated with major Rrenal (HR 5, 95% CI 2-18, p=0.002). Conclusions: Serum levels of NGAL were independent predictors of major renal response in MM patients with severe RI. Thus, serum NGAL could identify MM patients with severe RI who should be treated with more aggressive therapies and more effective and rapidly acting antimyeloma regimens. The absence of any predictive value of GDF-15 in MM-related severe RI in contrast to AL amyloidosis patients reflect the different biology of RI in these plasma cell dyscrasias. Figure Disclosures Dimopoulos: Sanofi Oncology: Research Funding. Kastritis:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genesis: Honoraria; Prothena: Honoraria; Pfizer: Honoraria; Takeda: Honoraria. Papassotiriou:Roche: Employment. Gavriatopoulou:Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses. Terpos:Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria.

Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs After Cardiac Surgery

To investigate the association of nonsteroidal anti-inflammatory drug (NSAID) administration with urinary neutrophil gelatinase-associated lipocalin (NGAL) levels in children following cardiopulmonary bypass (CPB) who did not develop acute kidney injury (AKI). In this prospective observational study, urinary NGAL levels were investigated in 210 children who underwent cardiothoracic surgery requiring CPB. Children with clinical AKI (defined as an increase in serum creatinine ≥50% from baseline within 72 hours of CPB) were excluded from the analysis. NSAIDs were administered no sooner than 24 hours after CPB. NGAL levels were compared between children who received NSAIDs (n = 146) and those who did not receive NSAIDs (n = 64). The median age was 3.2 years in the children who received NSAIDs and 2.5 years in those who did not receive NSAIDs (P = .05). Before NSAID administration at 24 hours following CPB, the median NGAL level was 15 ng/mL in both groups (P = .92). Following NSAID administration, the median urinary NGAL level increased to 83 ng/mL (IQR, 45-95 ng/mL) at 72 hours after CPB in those receiving NSAIDs (P < .001). In contrast, the median NGAL level decreased to 10 ng/mL (IQR, 5.4-15.9 ng/mL) at 72 hours after CPB in those who did not receive NSAIDs (P = .01). In multivariable analysis, children receiving NSAIDs demonstrated a 5-fold elevation of urinary NGAL levels at 60-72 hours following CPB compared with those who did not receive NSAIDs (P < .001). NSAID administration was associated with a significant increase in urinary NGAL in children who did not develop clinical AKI following CPB. This indicates that NGAL can detect NSAID-induced subclinical kidney injury in this population.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

To evaluate neutrophil gelatinase associated lipocalin (NGAL) in patients infected by hepatitis C virus (HCV) before and during treatment with directly acting antivirals (DAAs). NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate (eGFR). Then, NGAL and eGFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for non-parametric data. Differences in dichotomous variables were evaluated through χ (2) test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four (FIB-4), AST to platelet ratio index (APRI), and eGFR]. Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with eGFR < 60 mL/min vs patients with eGFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/dL were compared with those of NGAL ≤ 118.11 ng/dL, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis (P > 0.05). Linear correlation was found between NGAL and both age (P = 0.0475) and eGFR (P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for eGFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline (P = 0.0239). Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

A rapid plasma neutrophil gelatinase-associated lipocalin assay for diagnosis of acute pyelonephritis in infants with acute febrile urinary tract infections: a preliminary study

In infants with febrile urinary tract infection (UTI), the accurate rapid diagnosis of acute pyelonephritis (APN) would be valuable because early aggressive treatment reduces the risk of renal scarring. The objective of the study was to evaluate whether rapid plasma neutrophil gelatinase-associated lipocalin (NGAL) assay could be used as a diagnostic biomarker of renal parenchymal injury in infants with acute febrile UTI to distinguish APN at the bedside. This prospective observational study included 47 infants, who were admitted with a first episode of acute febrile UTI. Total UTI group was divided into the Cortical defect (UTI-CD, n = 24) group and Non-cortical defect (UTI-ND, n = 23) group, according to the result of renal scan. For the Control group, 15 infants who presented a febrile episode without any focus of bacterial infection were included. On admission, the median NGAL level (106.5 [60-476] ng/mL) in the UTI-CD group was significantly higher than that (60 [60-196] ng/mL) in the UTI-ND group and that (60 [60-197] ng/mL) in the Control group and was significantly decreased to 60 [60-306] ng/mL after an antibiotic treatment. The area under the receiver operating characteristic curves was 0.748 (95% CI, 0.610-0.887; P = 0.003) for NGAL levels and 0.724 (95% CI, 0.579-0.868; P = 0.009) for CRP levels. The best cutoff of NGAL level for detection of APN was founded to be 61.0ng/mL (sensitivity, 75.0%; specificity, 78.3%). Although not a stand-alone test, the rapid determination of plasma NGAL level provides valuable information quickly, concerning the distinction of APN, for determining the clinical course of acute febrile UTI.

Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants

BackgroundBronchopulmonary dysplasia (BPD) is a chronic lung disease mostly occurring in preterm infants. The pathogenesis of BPD involves early inflammation and remodeling of the premature lung. AimTo search for the novel predictive marker of BPD development, we studied serum levels of neutrophil gelatinase-associated lipocalin (NGAL), an innate immune mediator, in preterm infants. MethodsSerum NGAL concentrations at birth were measured by enzyme-linked immunosorbent assay. The reference levels were determined in 52 infants having no anomalies or inherited diseases. The levels and clinical variables were assessed in association with BPD. ResultsGeometric means (95%CI) of serum NGAL levels at birth of infants having no underlying diseases were 32.4 (22.1–47.5), 58.6 (47.9–71.8), and 126.2 (99.0–168.7) ng/mL for <31, 31–36 and >36 gestational weeks (GW), respectively (p<0.001). These levels positively correlated with neutrophil (p<0.0001) or monocyte counts (p<0.0001). The median NGAL levels (307.8ng/mL) and neutrophil counts (4141/μL) at birth of 16 preterm infants (<31GW) who developed BPD were higher than those (42.9ng/mL and 1357/μL) of 20 infants (<31GW) who did not (p<0.0001 and p=0.012), respectively. In multivariable analysis for 36 infants born less than 31GW, higher NGAL levels (≥82ng/mL) but not neutrophil counts at birth had a significant association with developing BPD (gestational-age adjusted odds ratio [OR]=37.45 [3.08–455.49], p<0.01). ConclusionsHigh serum levels of NGAL at birth could be an early sensitive marker for BPD in preterm infants, because their levels were physiologically low.

Prognostic Significance of Neutrophil Gelatinase–Associated Lipocalin in ST-Segment Elevation Myocardial Infarction

ObjectivesThis study investigated the prognostic value of neutrophil gelatinase–associated lipocalin (NGAL) in patients with ST-segment elevation myocardial infarction (STEMI).BackgroundNeutrophil gelatinase–associated lipocalin is a promising biomarker for acute kidney injury. Recently,...