Structural characterization of glycoprotein NGAL, an early predictive biomarker for acute kidney injury

Zhao, Cheng; Ozaeta, Panfilo; Fishpaugh, Jeffrey R.; Rupprecht, Kevin; Workman, Ryan; Grenier, Frank C.; Ramsay, Carol

doi:10.1016/j.carres.2010.07.024

Cited by 20 publications

(15 citation statements)

References 31 publications

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“…30 The rNGAL we used for recovery studies was predominantly monomeric but did contain dimers and this may account for the differences between assays depending on the specificity and affinity of the antibodies used for the various forms. 5,31 This would also be the case when measuring endogenous NGAL where although good agreement was largely seen between most assays, differences were apparent in some samples.…”

Section: Discussionmentioning

confidence: 99%

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine

et al. 2013

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Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury that is beginning to be used in clinical practice in addition to research studies. The current study describes an independent validation and comparison of five commercially available NGAL assays, focusing on urine samples. This is an essential step in the translation of this marker to clinical use in terms of allowing valid inter-study comparison and generation of robust results. Methods: Two CE (Conformité Europé enne)-marked assays, the NGAL Test (BioPorto) on Siemens ADVIA w 1800 and the ARCHITECT Urine NGAL assay on i2000SR (Abbott Laboratories), and three research-use-only (RUO) ELISAs (R&D Systems, Hycult and BioPorto) were evaluated. Imprecision, parallelism, recovery, selectivity, limit of quantitation (LOQ), vulnerability to interference and hook effect were assessed and inter-assay agreement was determined using 68 urine samples from patients with various renal diseases and healthy controls. Results: The Abbott and R&D Systems assays demonstrated satisfactory performance for all parameters tested. However for the other three assays evaluated, problems were identified with LOQ (BioPorto/ADVIA w ), parallelism (BioPorto ELISA) or several parameters (Hycult). Between-method agreement varied with the Hycult assay in particular being markedly different and highlighting issues with standardization and form of NGAL measured. Conclusions: Variability exists between the five NGAL assays in terms of their performance and this should be taken into account when interpreting results from the various clinical or research studies measuring urinary NGAL.

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Section: Discussionmentioning

confidence: 99%

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine

et al. 2013

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“…20 Initially, it was found in activated neutrophils 8 ; however, researchers found that NGAL may also be expressed in other cells such as in stomach, liver, and epithelial tissue under certain conditions 6,21 including renal tubular epithelial cells, which suffered various injuries. 8 Mishra et al compared the protective action of exogenous NGAL on renal mice 1 h before ischemia, during ischemia, 1 h after ischemia, and found that the action could prevent renal injury each of the three times. It was indicated that NGAL could play an important protective role during 1 h before ischemia and 1 h after ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Subsequently, it is also been found in other types of cells, including tubular cells of the kidney, which suffered various injuries. 8 As an acute phase protein, it is currently one of the interesting proteins involved in the phase of AKI. Recently experimented evidence indicates that exogenous NGAL could ameliorate the morphologic and functional consequences in a murine model of renal IRI and reduce the apoptotic tubule cell death, 9 which has led to the hypothesis that NGAL may prevent tubular injury.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

Zang

Wang

et al. 2012

Renal Failure

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We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) on rats ischemia/reperfusion (I/R) renal injury. Eighteen Sprague-Dawley male rats were randomly divided into three groups. Control group (n ¼ 6) suffered left unilateral nephrectomy, I/R þ NS (normal saline) (n ¼ 6) and I/R þ NGAL (n ¼ 6) group were subjected to 45 min right renal ischemia/24 h reperfusion after left unilateral nephrectomy. Serum creatinine (Scr) and blood urea nitrogen (Bun) were measured on automatic biochemistry analyzer; kidney sections were stained with hematoxylin-eosin; terminal dUTP nick-labeling method was used to examine the apoptosis of tubular epithelial cells; Cleaved caspase-3 and Bax protein expression were detected by immunohistochemistry and Western Blot; real-time polymerase chain reaction was used to detect the expression of Bax mRNA. Rats with NGAL displayed an attenuated renal damage and a decreased number of tubular epithelial cell apoptosis compared to the I/R þ NS group (Scr 63.400 AE 11.908 vs. 121.857 AE 17.151 μmol/L, Bun 14.840 AE 2.868 vs. 28.557 AE 6.434 mmol/L, apoptosis cell number 7.800 AE 1.924 vs. 15.400 AE 3.049/high power field (HPF), p < 0.05), the values were lower in the control group (24.000 AE 3.829 μmol/L, 5.814 AE 1.961 mmol/L, 1.800 AE 0.837/HPF, p < 0.05) compared to two groups above; NGALtreated rats showed down-regulated Cleaved caspase-3 protein (0.284 AE 0.066 vs. 0.409 AE 0.073, p < 0.05), Bax protein (0.346 AE 0.055 vs. 0.443 AE 0.041, p < 0.05), Bax mRNA (1.423 AE 0.187 vs. 2.550 AE 0.217, p < 0.05) compared to I/R þ NS group, but the values were higher in both of the two groups than those in the control group (Cleaved caspase-3 protein 0.104 AE 0.029, Bax protein 0.155 AE 0.027, Bax mRNA 1.000 AE 0.000, p < 0.05). We supposed that exogenous NGAL can inhibit the activation of caspase-3, reduce the expression of Bax, and thus reduce renal tubular cell apoptosis and protect renal function in I/R injury rats.

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“…It was initially found in activated neutrophils, and found in other types of cells, including the renal tubular cells after a variety of injuries (Zhao et al, 2010). Mishra et al (2004) compared the protective effects of exogenous NGAL on the kidneys, which was administered 1 h before ischemia, at ischemia and 1 h after ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that the incidence rate of AKI in all hospitalized patients is 5-35%, and the mortality is increased 2-to 5-fold (Kanbay et al, 2010). Through gene analysis of the biological processes of ischemic AKI, it was found that neutrophil gelatinase-associated lipocalin (NGAL) was one of the gene products that were clearly expressed early after the renal ischemic injury (Zhao et al, 2010). Investigators have demonstrated that the administration of exogenous NGAL could significantly reduce the morphological and functional damages in murine renal ischemia-reperfusion (I/R), and reduce number of the apoptotic renal tubular cells (Mishra et al, 2004), where apoptosis has been considered to be the major form of death of renal tubular epithelial cells after renal ischemic injury (Dagher, 2004).…”

Section: Introductionmentioning

confidence: 99%

In vivo mechanism study of NGAL in rat renal ischemia-reperfusion injury

Zang

Zhang

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This study aimed to determine the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) in rat kidney on ischemia/reperfusion injury (I/R). The rat I/R model was set up by cutting one kidney and clamping the contralateral renal pedicle for 45 min. Male SD rats were randomly divided into sham-operation, I/R and NGAL groups. Hematoxylin-eosin staining was performed to observe the renal pathological changes in the 3 groups; serum creatinine (Scr) and blood urea nitrogen (BUN) determined in blood samples taken from the inferior vena cava 24 h after the reperfusion were measured; TUNEL was used to observe the apoptosis of renal tubular epithelial cells; immunohistochemistry was performed to evaluate the expressions of Bax and activated caspase-3; Western blotting was used to determine the expression changes in apoptotic proteins Fas and Bcl-2. Compared with the I/R group, Scr and BUN of the NGAL group were 63.400 ± 11.908 vs 121.857 ± 17.151 µM and 14.840 ± 2.868 vs 28.557 ± 6.434 mM, respectively. The number of apoptotic tubular epithelial cells was reduced (7.800 ± 1.924 vs 15.400 ± 3.049); the expression of 8741 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 8740-8748 (2014) Study of NGAL in renal ischemia-reperfusion injury renal tissue Fas mRNA of the NGAL group was decreased (2.34 ± 0.51 vs 6.84 ± 2.34); the expression of the Bax protein was lower (7.440 ± 1.640 vs 15.456 ± 1.955%); the expression of the CC3 protein was decreased (3.171 ± 0.321 vs 7.291 ± 1.059%), while the expression of the Bcl-2 protein increased (6.91 ± 1.64 vs 5.30 ± 1.48), P < 0.05. NGAL had a protective effect towards the renal tubular epithelial cells in I/R, and the effect might have been associated with the reduction in apoptosis and the altered expression of apoptotic proteins, which would thereby reduce tissue damage and protect the kidney.

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Structural characterization of glycoprotein NGAL, an early predictive biomarker for acute kidney injury

Cited by 20 publications

References 31 publications

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine

Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

In vivo mechanism study of NGAL in rat renal ischemia-reperfusion injury

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