Neutrophil Gelatinase Associated Lipocalin 
(NGAL) – a biomarker of renal dysfunction in patients 
with liver cirrhosis: Do we have enough proof?

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Abstract

Rationale. Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker.

Objective. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis.

Methods and results. We have searched through current literature and analyzed all significant full text articles on this topic.

Discussions. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.

Abbreviations: ADQI = Acute Dialysis Quality Initiative, AKI = acute kidney injury, AKIN = Acute Kidney Injury Network, ATN = acute tubular necrosis, CKD = chronic kidney disease, Cys C = cystatin C, GFR = glomerular filtration rate, HRS = hepatorenal syndrome, IAC = International Ascites Club, IL-18 = interleukin-18, KIM-1 = kidney injury molecule-1, L-FABP = liver-type fatty acid-binding protein, LT = liver transplantation, MDRD6 = Modification of Diet in Renal Disease 6, NAG = N-acetyl-β-D-glucosaminidase, NGAL = Neutrophil Gelatinase-Associated Lipocalin, pi-GST = pi-glutathione S-transferase, PRA = prerenal azotemia, RBP = retinol binding protein, RRT = renal replacement therapies, SCr = serum creatinine, SLKT = simultaneous liver and kidney transplant, UO = urine output, γ-GT = γ-glutamyl transpeptidase

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Most cited references 29

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Dual action of neutrophil gelatinase-associated lipocalin.

Kai M Schmidt-Ott, Kiyoshi Mori, Jau Yi Li … (2007)

Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.

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Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness.

Michael B. Bennett, Sean Bagshaw, Hiroshi Morimatsu … (2010)

Sepsis is the most common trigger for acute kidney injury (AKI) in critically ill patients. We sought to determine whether there are unique patterns to plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in septic compared with non-septic AKI. Prospective observational study. Two adult ICUs in Melbourne, Australia. Critically ill patients with septic and non-septic AKI. None. Blood and urine specimens collected at enrollment, 12, 24 and 48 h to measure plasma and urine NGAL. Eighty-three patients were enrolled (septic n = 43). Septic AKI patients had more co-morbid disease (p = 0.005), emergency surgical admissions (p < 0.001), higher illness severity (p = 0.008), more organ dysfunction (p = 0.008) and higher white blood cell counts (p = 0.01). There were no differences at enrollment between groups in AKI severity. Septic AKI was associated with significantly higher plasma (293 vs. 166 ng/ml) and urine (204 vs. 39 ng/mg creatinine) NGAL at enrollment compared with non-septic AKI (p < 0.001). Urine NGAL remained higher in septic compared with non-septic AKI at 12 h (p < 0.001) and 24 h (p < 0.001). Plasma NGAL showed fair discrimination for AKI progression (area under receiver-operator characteristic curve 0.71) and renal replacement therapy (AuROC 0.78). Although urine NGAL performed less well (AuROC 0.70, 0.70), peak urine NGAL predicted AKI progression better in non-septic AKI (AuROC 0.82). Septic AKI patients have higher detectable plasma and urine NGAL compared with non-septic AKI patients. These differences in NGAL values in septic AKI may have diagnostic and clinical relevance as well as pathogenetic implications.

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Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery.

Won K Han, Gebhard Wagener, Yanqing Zhu … (2009)

Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery. Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI. Thirty-six patients developed AKI, defined as an increase in Scr of > or =0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively. The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.

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Author and article information

Journal

Journal ID (nlm-ta): J Med Life

Journal ID (iso-abbrev): J Med Life

Journal ID (publisher-id): JMedLife

Title: Journal of Medicine and Life

Publisher: Carol Davila University Press (Romania )

ISSN (Print): 1844-122X

ISSN (Electronic): 1844-3117

Publication date (Print): 2015

Volume: 8

Issue: Spec Issue

Pages: 15-20

Affiliations

[* ]Department of Medical Sciences I, University of Medicine and Pharmacy Craiova, Romania

[** ]Department of Medical Sciences II, University of Medicine and Pharmacy Craiova, Romania

[*** ]Department of Biochemistry, University of Medicine and Pharmacy Craiova, Romania

Author notes

Correspondence to: Firu Ștefan George, PhD student, Department of Medical Sciences I, University of Medicine and Pharmacy Craiova, Romania. 2 Petru Rares Street, Craiova, Dolj, code 200349, Romania, Mobile phone: +40760 311 379, E-mail: firustefangeorge@yahoo.com

Article

Publisher ID: JMedLife-08-15

PMC ID: 4564045

SO-VID: f0f4a46c-9e99-4cea-adae-2ec9cfefc90c

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Neutrophil Gelatinase Associated Lipocalin (NGAL) – a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

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Most cited references 29

Dual action of neutrophil gelatinase-associated lipocalin.

Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness.

Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery.

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