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Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. 2010

Subhankar Chakraborty, and Sukhwinder Kaur, and Venkata Muddana, and Neil Sharma, and Uwe A Wittel, and Georgios I Papachristou, and David Whitcomb, and Randall E Brand, and Surinder K Batra
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

OBJECTIVE About 210,000 new cases of acute pancreatitis (AP) involving reversible inflammation of the pancreas are reported in the United States every year. About one-fourth of all patients with AP go on to develop severe acute pancreatitis (SAP), which, unlike uncomplicated or mild acute pancreatitis (MAP, usually a self-limiting disease), constitutes a life-threatening condition with systemic complications, chiefly multiorgan dysfunction. An early prediction of the severity and outcome of patients with acute pancreatitis (AP) can lead to better treatment regimens for patients with SAP. There is currently no established biomarker for the early diagnosis of SAP. In this study, we investigated the potential of serum neutrophil gelatinase-associated lipocalin (NGAL) as an early marker to distinguish severe (SAP) from MAP and examine its ability to predict the prognosis of patients with SAP. METHODS To check the time kinetics of rise in NGAL during AP, we quantified NGAL levels in sera from mice with MAP or SAP at various time points (6, 12, 24 and 48 h) using sandwich enzyme-linked immunosorbent assay. NGAL levels were also quantified in serum from 28 MAP and 16 SAP cases and compared with 28 chronic pancreatitis and 30 healthy control samples. Samples collected within 5 days from onset of symptoms were included. The relationship of NGAL levels with survival and multiorgan failure (MOF) in SAP was also examined. RESULTS Although NGAL levels were significantly higher in mice with both MAP and SAP 6 h after induction (compared to control animals), only mice with SAP exhibited a significant increase in NGAL levels at 24 h (P=0.003). NGAL levels declined at 48 h after induction in animals with both MAP and SAP but did not reach baseline levels. Among patients, mean (+/-s.e.) serum NGAL level was significantly higher in SAP (634+/-139 ng/ml) compared to MAP (84.7+/-7 ng/ml, P=0.0001). On subanalysis, the difference between MAP and SAP cases was significant in the first 48 h but not at 72, 96, or 120 h. NGAL was 100%, 96%, 97%, and 84% specific and 100%, 87.5%, 92%, and 94% sensitive in distinguishing SAP from MAP at 48, 72, 96, and 120 h, respectively, after the onset of symptoms. NGAL levels were significantly higher in SAP cases complicated by MOF (P=0.004), and high NGAL levels in SAP appeared to correlate with a fatal outcome. CONCLUSIONS Our data provide the first evidence for the potential of serum NGAL as an early marker to distinguish MAP from SAP. Further, high NGAL levels predict MOF and fatal outcome in patients with SAP. This study provides sufficient evidence for multi-institutional randomized trials for estimating the potential of NGAL as early biomarker for SAP.

UI MeSH Term Description Entries
D008297 Male Males
D010195 Pancreatitis INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis. Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D011237 Predictive Value of Tests In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test. Negative Predictive Value,Positive Predictive Value,Predictive Value Of Test,Predictive Values Of Tests,Negative Predictive Values,Positive Predictive Values,Predictive Value, Negative,Predictive Value, Positive
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071068 Lipocalin-2 A lipocalin of approximately 200 amino acids that functions as an iron transporter and is expressed by cells of BONE MARROW and many other cells with secretory functions. It is involved in APOPTOSIS and may function to limit pathogenic bacterial growth as part of the INNATE IMMUNE RESPONSE. Lipocalin-2 Protein,NGAL Protein,Neutrophil Gelatinase-Associated Lipocalin,Oncogene 24p3 Protein,Siderocalin Protein,Lipocalin 2,Lipocalin 2 Protein,Neutrophil Gelatinase Associated Lipocalin
D000209 Acute-Phase Proteins Proteins that are secreted into the blood in increased or decreased quantities by hepatocytes in response to trauma, inflammation, or disease. These proteins can serve as inhibitors or mediators of the inflammatory processes. Certain acute-phase proteins have been used to diagnose and follow the course of diseases or as tumor markers. Acute Phase Reactant,Acute-Phase Glycoprotein,Acute-Phase Reactant,Acute-Phase Reactants,Proteins, Acute-Phase,Reactants, Acute-Phase,Acute-Phase Glycoproteins,Acute-Phase Protein,Acute Phase Glycoprotein,Acute Phase Glycoproteins,Acute Phase Protein,Acute Phase Proteins,Acute Phase Reactants,Glycoprotein, Acute-Phase,Glycoproteins, Acute-Phase,Phase Reactant, Acute,Protein, Acute-Phase,Proteins, Acute Phase,Reactant, Acute Phase,Reactant, Acute-Phase,Reactants, Acute Phase

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