Dual Action of Neutrophil Gelatinase–Associated Lipocalin

Schmidt‐Ott, Kai M.; Mori, Kiyoshi; Li, Jau Yi; Kalandadze, Avtandil; Cohen, David J.; Devarajan, Prasad; Barasch, Jonathan

doi:10.1681/asn.2006080882

Cited by 677 publications

(645 citation statements)

References 39 publications

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“…It has been reported that kidney epithelia express and excrete large quantities of NGAL into urine following acute injury, reaching up to 1000‐fold induction of NGAL mRNA and protein in the most severe cases 33. There is a large body of literature to indicate that uNGAL increases during the first posttransplant week in renal transplant recipients with DGF, especially in the very early urine samples collected within six h postsurgery 34, 35, 36.…”

Section: Urinary Ngal and Dgfmentioning

confidence: 99%

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

et al. 2017

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Neutrophil gelatinase‐associated lipocalin (NGAL), a protein belonging to the lipocalin superfamily initially found in activated neutrophils, is expressed by several cell types, including kidney tubule. The increase in NGAL production and release from tubular cells in response to various insults has been proven to predict acute kidney injury (AKI). For this reason, it has emerged as a valuable noninvasive biomarker of AKI in clinical nephrology. Also in the renal transplant setting, different studies have indicated NGAL as a valuable tool, especially in the early postoperative period, since the currently available clinical and laboratory parameters remain poorly sensitive to monitor immediate posttransplant graft function. This is an analysis of the recent literature to assess the utility of plasma and urinary NGAL, exosomal mRNA for NGAL, and NGAL levels in the perfusate of machine‐perfused kidneys for the prediction of graft function recovery in the early postsurgery phase after renal transplantation. We found that NGAL appears as a promising troponin‐like biomarker to detect short‐term impairment of graft function after renal transplant, but there are still some limitations in its clinical application, essentially related to its low specificity. Moreover, comparing NGAL assayed in serum, urine, machine‐perfusate, or as exosomal mRNA, each one has shown limitations and benefits in terms of predictive performance for DGF, according to various existing studies, feasibly due to different cut‐off levels, designs and patient sample sizes.

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Section: Urinary Ngal and Dgfmentioning

confidence: 99%

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

et al. 2017

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“…However, NGAL is also expressed in the uterus, prostate gland, salivary glands, bone marrow, stomach, colon, trachea, lungs, liver, and kidneys 6. With its siderophore‐chelating property, NGAL is considered to be a bacteriostatic agent 7. In addition, NGAL has been shown to be involved in the attenuation of apoptosis and the enhancement of the proliferative response 8…”

mentioning

confidence: 99%

Neutrophil Gelatinase–Associated Lipocalin in Dogs with Naturally Occurring Renal Diseases

Hsu

Lin

et al. 2014

Veterinary Internal Medicne

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BackgroundNeutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail.Hypothesis/ObjectivesThe goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease.AnimalsClient‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined.MethodsSerum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively.ResultsSerum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time.Conclusion sNGAL is a useful prognostic marker when evaluating dogs with CKD.

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“…Articles as well as in neutrophils and macrophages (16,17). NGAL expression is up-regulated by infection, inflammation, ischemia, and neoplastic transformation (18)(19)(20)(21)(22)(23).…”

Section: Ungal As Biomarker For Late-onset Sepsismentioning

confidence: 99%

“…Filtered NGAL is captured by megalin in the proximal tubule and degraded; thus, very little (0.1-0.2%) is found in urine, suggesting that systemic (filtered) NGAL contributes little if any NGAL to the urinary pool. In the postischemic mouse model, NGAL production is up-regulated within the kidney in the thick ascending limb of Henle and the collecting ducts (17). Studies looking at the biomarker characteristics of NGAL using the NGAL-reporter mouse model have also demonstrated the α-intercalated cells of the collecting system and the thick ascending limb of Henle as the sources of urinary NGAL (24).…”

Section: Ungal As Biomarker For Late-onset Sepsismentioning

confidence: 99%

Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis

et al. 2015

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Background:To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. Methods: This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. results: The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. conclusion: UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.l ate-onset sepsis, by definition, occurs at >72 h of life and can affect as many as 20-30% of infants hospitalized in the neonatal intensive care unit (NICU), with varying mortality rates depending on gestational age (GA) (1,2). Accurate diagnosis of late-onset sepsis in this vulnerable population can be difficult due to nonspecific signs and symptoms, as well as due to difficulties in obtaining sufficient diagnostic specimens, such as an adequate volume of blood samples. In order to determine which infants are most likely to be infected, biomarkers have been utilized with varying success. The ideal biomarker should have rapid onset of expression, reversibility of expression when the disease abates, ease of collection and measurement, high sensitivity, and high negative predictive value (NPV). Currently, C-reactive protein (CRP) is the most frequently used serum biomarker in the NICU population. As described by Benitz et al. (3), a single CRP at the time of a sepsis evaluation has a modest sensitivity (65%) and NPV (79%). In septic infants, CRP peaks 24-48 h after the onset of symptoms; a second sample obtained during this time period increases the sensitivity to 97%. Although CRP can help determine which neonates may not be septic, it is a relatively invasive, late biomarker and the results of the second sample may have limited additional diagnostic utility compared with blood culture results, which are often available about the same time. A noninvasive biomarker with high sensitivity, high NPV, and results available at the time of sepsis evalu...

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Dual Action of Neutrophil Gelatinase–Associated Lipocalin

Cited by 677 publications

References 39 publications

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

Neutrophil Gelatinase–Associated Lipocalin in Dogs with Naturally Occurring Renal Diseases

Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis

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