Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection

Ichino, Masatsugu; Kuroyanagi, Yoko; Kusaka, Mamoru; Mori, Terumi; Ishikawa, Kiyohito; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka

doi:10.1016/j.juro.2009.01.010

Cited by 53 publications

(42 citation statements)

References 19 publications

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“…Further, we observed that plasma NGAL levels could differentiate APN from a lower UTI and predict the treatment response of pediatric UTIs. In accordance with our findings, renal NGAL mRNA and protein levels have been shown to increase soon after bacterial injections in an experimental rat UTI model (17). Hatipoglu et al (29) showed significantly higher levels of urine matrix metalloproteinase-9/NGAL/ Cr in children with UTIs compared to those in children with contaminated urine.…”

Section: Discussionsupporting

confidence: 91%

“…Recent studies have also shown a possible association between increased NGAL levels and UTIs. Ichino et al (17) demonstrated experimentally that uNGAL levels in rats increased in both the early and extensive fibrosis stages of pyelonephritis, suggesting that uNGAL might also be useful as a marker of APN and renal scarring in humans. Indeed, we, and other investigators, have demonstrated that uNGAL can be a useful predictor for detecting UTIs in children (1,18).…”

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Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections

et al. 2015

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Background:The identification of acute pyelonephritis (APN) is still a challenge. Methods: Patients admitted for their first urinary tract infection (UTI) were enrolled. Plasma neutrophil gelatinaseassociated lipocalin (NGAL) levels were measured at admittance and after treatment. Laboratory, clinical, and imaging results were compared between children with and without APN. results: A total of 123 patients were enrolled (53 APN and 70 lower UTI). After adjusting for age and gender, plasma NGAL levels were higher in the APN group than in the lower UTI group (233 (129-496) ng/ml vs. 71 (50.8-110) ng/ml, P < 0.001). NGAL levels were correlated with the serum levels of leukocytes, C-reactive protein, and creatinine, as well as fever duration (P < 0.05). Multivariable analysis revealed that logtransformed plasma NGAL was an independent predictor of APN (P < 0.05). Receiver operating curve analysis showed a good diagnostic profile of NGAL for identifying APN (area under the curve 0.864) with a best cut-off value of 102.5 ng/ml. The NGAL levels in both two groups decreased after treatment compared to levels before treatment (P < 0.001). conclusion: Plasma NGAL can be a sensitive predictor for identifying APN and monitoring the treatment response of pediatric UTI. u rinary tract infections (UTIs) are among the most common bacterial infections in children (1). Early detection and proper management of UTIs is important since UTIs involving the kidney may cause permanent renal scarring and be a risk factor for future development of renal insufficiency (2). Establishing the diagnosis of acute pyelonephritis (APN) requires imaging with 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy to view renal parenchymal involvement (3). Although a DMSA scan is considered to be very sensitive in the assessment of renal damage, it is expensive, not readily available in all centers, and exposes the patients to radiation (4). Therefore, a more practical and accessible tool to determine the presence of renal parenchymal involvement could be helpful for the timely management of UTIs.Neutrophil gelatinase-associated lipocalin (NGAL), as a member of the lipocalin superfamily, is produced from the nephron in response to tubular epithelial damage (5). It has been identified as one of the earliest and potentially one of the most indicative biomarkers of acute kidney injury (AKI) from a diverse array of conditions and can differentiate between prerenal and intrinsic causes (6,7). Urinary NGAL (uNGAL) levels increase in patients with different causes of nephropathies (8,9) and might be a valuable tool in monitoring the treatment response of various renal diseases (10,11).As an iron-carrier protein derived from human neutrophils, NGAL also plays an important role in the innate immune response to bacterial infection (12). Experimentally, NGAL was capable of blocking Escherichia coli growth under ironpoor conditions, but NGAL with siderophore iron was not (13). NGAL-knockout mice demonstrated substantially increased mortality after intraperitoneal i...

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections

et al. 2015

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“…It has been demonstrated that NGAL is released by activated neutrophils of the infected host and prevents bacterial iron uptake consuming the ambient iron and thus reduce bacterial growth [5,6]. Recent studies revealed that uNGAL is increased in acute kidney injury (AKI) induced by nephrotoxins or ischemia, and it has been speculated that NGAL expression was induced in order to contribute to tissue regeneration after kidney damage [10,13]. Similarly, expression of NGAL increases as a part of the immune response to remove bacteria in the early stage of infection.…”

Section: Discussionmentioning

confidence: 99%

“…Serum level of NGAL has been measured in human studies, and it has been reported that serum NGAL level is a useful marker to distinguish acute bacterial from viral infection in newborns, children, and adults [7][8][9]. Recently, Ichino et al [10] constituted an experimental pyelonephritis in rats and established that urine level of NGAL in rats increased in the early stage of UTI, suggesting that urine NGAL (uNGAL) might be used to predict UTI in humans as well.…”

Section: Introductionmentioning

confidence: 99%

Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin

Yılmaz¹,

et al. 2009

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Neutrophil gelatinase associated lipocalin (NGAL) is a protein identified in human neutrophil granules. The aim of the study was to assess whether urine level of NGAL (uNGAL) could represent a novel, reliable marker of urinary tract infection (UTI) and to determine the optimal cutoff level for uNGAL to predict UTI in children. Sixty patients with symptomatic UTI and 29 healthy controls were enrolled the study. Urine NGAL was measured by enzyme-linked immunosorbent assay. A dimercaptosuccinic acid (DMSA) radionuclide scan was performed within 7 days in the patients with UTI in an attempt to distinguish pyelonephritis from cystitis. Mean uNGAL level was significantly higher in the UTI group than in the controls (91.02 ng/ml vs 14.29 ng/ml, p = 0.0001) and using a cutoff 20 ng/ml for uNGAL for diagnosis of UTI, sensitivity, and specificity were 97% and 76%, respectively [area under the curve (AUC): 0.979]. Mean uNGAL/creatinine ratio (uNGAL/Cr) was also significantly higher in the UTI group [201.81 ng/mg creatinine (Cr) vs 18.08 ng/mg Cr; p = 0.0001], and using a cutoff 30 ng/mg Cr for uNGAL/Cr for diagnosis of UTI, sensitivity and specificity were 98% and 76%, respectively (AUC: 0.992). In conclusion, both uNGAL and uNGAL/Cr can be used as a novel, sensitive marker for early prediction of UTI in the absence of acute kidney injury and chronic kidney disease, and the optimal cutoff value for prediction of UTI is lower than the values determined for acute kidney injury. Further investigations with larger patient groups are required to confirm our results.

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“…A few studies have suggested that NGAL could discriminate the severity of infection in children, in kidney grafts and in a mouse model [4][5][6]. Therefore, in January-December 2011, we obtained a urine sample for NGAL in 50 patients (46 females and 4 males) hospitalized in our setting who underwent MR within 1 week from hospitalization for clinical suspicion of APN.…”

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The search for perfect biomarkers in acute kidney damage: the case of NGAL, from AKI to acute pyelonephritis: back to the clinic?

Piccoli

Ferraresi

Aroasio

et al. 2012

Nephrology Dialysis Transplantation

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Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection

Abstract: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.

Cited by 53 publications

References 19 publications

Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections

Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections

Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin

The search for perfect biomarkers in acute kidney damage: the case of NGAL, from AKI to acute pyelonephritis: back to the clinic?

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