Elevated Serum Neutrophil Gelatinase-Associated Lipocalin Is an Early Predictor of Severity and Outcome in Acute Pancreatitis

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 declinedx 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.

New Biomarkers for Diagnosing Inflammatory Bowel Disease and Assessing Treatment Outcomes

“…While Lcn-2 correlates with other markers of inflammation, it does not appear to significantly distinguish between UC and CD. 43 Furthermore, Lcn-2 can be elevated in other conditions such as kidney disease, 44 ovarian cancer, 45 acute pancreatitis, 46 Chronic Obstructive Pulmonary Disease (COPD), 47 and cardiovascular disease 48 which limits its utility as an IBD specific biomarker.…”

Neutrophil Gelatinase-Associated Lipocalin, Macrophage Inhibitory Cytokine 1, and Carbohydrate Antigen 19-9 in Pancreatic Juice

“…Pancreatic disease is highly prevalent in Western countries, with a combined annual incidence of more than 2 million people in the United States alone [1–3]. Pancreatic diseases are clinically difficult to conclusively diagnose, as signs and symptoms consistent with a particular pancreatic etiology frequently overlap with multiple others, as is the case with chronic pancreatitis (CP) and pancreatic cancer (PC), to name a few.…”

Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity

“…Over the last few years, several studies have identified induction of NGAL in acute and chronic kidney injury, cardiovascular disease, transplantation, sepsis, chronic obstructive pulmonary disease, pancreatitis, and various cancers [8,16,17]. These findings raise intriguing questions about its correlation with the magnitude of inflammatory response as well as its specificity and sensitivity in assessing various inflammatory conditions.…”