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

Subhankar Chakraborty, Sukwinder Kaur, Venkata Muddana, Neil Sharma, Uwe A. Wittel, Georgios I. Papachristou, David Whitcomb, Randall E. Brand, Surinder Kumar Batra

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Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)2050-2059
Number of pages10
JournalAmerican Journal of Gastroenterology
Volume105
Issue number9
DOIs
StatePublished - Sep 1 2010

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Pancreatitis
Serum
Lipocalin-2
Fatal Outcome
Biomarkers

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. / Chakraborty, Subhankar; Kaur, Sukwinder; Muddana, Venkata; Sharma, Neil; Wittel, Uwe A.; Papachristou, Georgios I.; Whitcomb, David; Brand, Randall E.; Batra, Surinder Kumar.

In: American Journal of Gastroenterology, Vol. 105, No. 9, 01.09.2010, p. 2050-2059.

Research output: Contribution to journalArticle

Chakraborty, Subhankar ; Kaur, Sukwinder ; Muddana, Venkata ; Sharma, Neil ; Wittel, Uwe A. ; Papachristou, Georgios I. ; Whitcomb, David ; Brand, Randall E. ; Batra, Surinder Kumar. / Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. In: American Journal of Gastroenterology. 2010 ; Vol. 105, No. 9. pp. 2050-2059.
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abstract = "Objectives: 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.",
author = "Subhankar Chakraborty and Sukwinder Kaur and Venkata Muddana and Neil Sharma and Wittel, {Uwe A.} and Papachristou, {Georgios I.} and David Whitcomb and Brand, {Randall E.} and Batra, {Surinder Kumar}",
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T1 - Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis

AU - Chakraborty, Subhankar

AU - Kaur, Sukwinder

AU - Muddana, Venkata

AU - Sharma, Neil

AU - Wittel, Uwe A.

AU - Papachristou, Georgios I.

AU - Whitcomb, David

AU - Brand, Randall E.

AU - Batra, Surinder Kumar

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Objectives: 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.

AB - Objectives: 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.

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