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Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

ABSTRACT: Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R²?=?0.273; Spearman rho?=?0.581; P?2?=?0.132; Spearman rho?=?0.455, P?

SUBMITTER: Skouras C

PROVIDER: S-EPMC5037401 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

Skouras Christos C Zheng Xiaozhong X Binnie Margaret M Homer Natalie Z M NZ Murray Toby B J TB Robertson Darren D Briody Lesley L Paterson Finny F Spence Heather H Derr Lisa L Hayes Alastair J AJ Tsoumanis Andreas A Lyster Dawn D Parks Rowan W RW Garden O James OJ Iredale John P JP Uings Iain J IJ Liddle John J Wright Wayne L WL Dukes George G Webster Scott P SP Mole Damian J DJ

Scientific reports 20160927

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concent ...[more]

PMID: 27669975

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Project description:BackgroundRecent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP).MethodsWe retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients.ResultsThrough stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777.ConclusionsThe increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.

Dataset Information

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

Publications

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

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