Advertisement

Plasma level of soluble urokinase plasminogen activator receptor (suPAR) predicts long-term mortality after first acute alcohol-induced pancreatitis

      Highlights

      • P-suPAR is a prognostic marker of long-term mortality after first acute alcohol-induced pancreatitis
      • P-suPAR levels do not predict the recurrence of acute alcohol-induced pancreatitis
      • P-suPAR may help in detection of patients with highest risk for mortality after first acute alcohol-induced pancreatitis

      Abstract

      Background

      Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker associated with inflammatory and certain malignancies. Earlier we have shown that plasma suPAR (P-suPAR) predicts severity of acute alcohol-induced pancreatitis (AAP) on admission. Our aim was to investigate whether P-suPAR levels predict AAP recurrences or mortality during long-term follow-up after first AAP.

      Methods

      Eighty-three patients (median age 47.5, range 25–71 years) suffering their first AAP during 2001–2005 were recruited and followed prospectively for 9 years with a median follow-up time of 7.0 (range 0.3–9.8) years. P-suPAR was measured by enzyme-linked immunosorbent assay (ELISA) from the samples taken at follow-up visits. Survival was registered in November 2014.

      Results

      P-suPAR level on admission or after recovery of the first AAP did not predict the recurrence of AAP. However, higher P-suPAR measured after recovery of first AAP (3.6 vs. 2.9 ng/mL) predicted mortality during follow-up period (hazard ratio 1.48, p = .008). Cut-off value for P-suPAR indicating a higher risk for 10-year mortality resulted a value of ≥3.4 ng/mL. When adjusted for other covariates, P-suPAR above cut-off level retained its statistical significance as an independent factor.

      Conclusions

      P-suPAR level on admission or after recovery of the first AAP does not predict the recurrence of AAP during long-term follow-up. However, P-suPAR ≥3.4 mg/mL measured after recovery from first AAP is associated with an increased risk of 10-year mortality as an independent factor. This can be used to detect patients with highest risk after AAP, in order to focus the preventive healthcare actions.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Roberts S.E.
        • Morrison-Rees S.
        • John A.
        • Williams J.G.
        • Brown T.H.
        • Samuel D.G.
        The incidence and aetiology of acute pancreatitis across Europe.
        Pancreatology. 2017; 17: 155-165
        • Jaakkola M.
        • Nordback I.
        Pancreatitis in Finland between 1970 and 1989.
        Gut. 1993; 34: 1255-1260
        • Pelli H.
        • Sand J.
        • Laippala P.
        • Nordback I.
        Long-term follow-up after the first episode of acute alcoholic pancreatitis: time course and risk factors for recurrence.
        Scand J Gastroenterol. 2000; 35: 552-555
        • Pelli H.
        • Lappalainen-Lehto R.
        • Piironen A.
        • Sand J.
        • Nordback I.
        Risk factors for recurrent acute alcohol-associated pancreatitis: a prospective analysis.
        Scand J Gastroenterol. 2008; 43: 614-621
        • Talamini G.
        • Vaona B.
        • Bassi C.
        • Bovo B.
        • Damoc T.
        • Mastromauro M.
        • et al.
        Alcohol intake, cigarette smoking, and body mass index in patients with alcohol-associated pancreatitis.
        J Clin Gastroenterol. 2000; 31: 274-275
        • Thunø M.
        • Macho B.
        • Eugen-Olsen J.
        SuPAR: the molecular crystal ball.
        Dis Markers. 2009; 27: 157-172
        • Haupt T.
        • Kallemose T.
        • Ladelund S.
        • Rasmussen L.J.H.
        • Thorball C.W.
        • Andersen O.
        • et al.
        Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in general population.
        Biomark Insights. 2014; 9: 91-100
        • Nikkola A.
        • Aittoniemi J.
        • Huttunen R.
        • Rajala L.
        • Nordback I.
        • Sand J.
        • et al.
        Plasma level of soluble urokinase-type plasminogen activator receptor predicts the severity of acute alcohol pancreatitis.
        Pancreas. 2017; 46: 77-82
        • Banks P.A.
        • Bollen T.L.
        • Dervenis C.
        • Gooszen H.G.
        • Johnson C.D.
        • Sarr M.G.
        • et al.
        Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus.
        Gut. 2013; 62: 102-111
        • Stephens R.W.
        • Nielsen H.J.
        • Christensen I.J.
        • Thorlacius-Ussing O.
        • Sørensen S.
        • Danø K.
        • et al.
        Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis.
        J Natl Cancer Inst. 1999; 91: 869-874
        • Riisbro R.
        • Christensen I.J.
        • Nielsen H.J.
        • Brunner N.
        • Nilbert M.
        • Fernebro E.
        Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-receptor and Biomarker Group collaboration.
        Int J Biol Markers. 2005; 20: 93-102
        • Kolho K.L.
        • Valtonen E.
        • Rintamäki H.
        • Savilahti E.
        Soluble urokinase plasminogen activator receptor suPAR as a marker for inflammation in pediatric inflammatory bowel disease.
        Scand J Gastroenterol. 2012; 47: 951-955
        • Zimmermann H.W.
        • Koch A.
        • Seidler S.
        • Trautwein C.
        • Tacke F.
        Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis.
        Liver Int. 2012; 3: 500-509
        • Fidan E.
        • Mentese A.
        • Ozdemir F.
        • Deger O.
        • Kavgaci H.
        • Caner Karahan S.
        • et al.
        Diagnostic and prognostic significance of CA IX and suPAR in gastric cancer.
        Med Oncol. 2013; 2: 1-5
        • Tarui T.
        • Mazar A.
        • Cines D.
        • Takada Y.
        Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction.
        J Biol Chem. 2001; 276: 3983-3990
        • Huttunen R.
        • Syrjänen J.
        • Vuento R.
        • Hurme M.
        • Huhtala H.
        • Laine J.
        • et al.
        Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study.
        J Intern Med. 2011; 270: 32-40
        • Haupt T.H.
        • Petersen J.
        • Ellekilde G.
        • Klausen H.H.
        • Thorball C.W.
        • Eugen-Olsen J.
        • et al.
        Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study.
        Crit Care. 2012; 16: R130
        • Eugen-Olsen J.
        • Andersen O.
        • Linneberg A.
        • Ladelund S.
        • Hansen T.W.
        • Langkilde A.
        • et al.
        Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population.
        J Intern Med. 2010; 268: 296-308
        • Ventorp F.
        • Gustafsson A.
        • Träskman-Bendz L.
        • Westrin A.
        • Ljunggren L.
        Increased soluble urokinase-type plasminogen activator receptor (suPAR) levels in plasma of suicide attempters.
        PLoS One. 2015; 10e0140052
        • Borges G.
        • Cherpitel C.J.
        • Medina-Mora M.E.
        • Mondragón L.
        Violence related injuries in the emergency room: alcohol, depression, and conduct problems.
        Subst Use Misuse. 2004; 39: 911-930
        • Jaakkola M.
        • Sillanaukee P.
        • Löf K.
        • Koivula T.
        • Nordback I.
        Amount of alcohol is an important determinant of the severity of acute alcoholic pancreatitis.
        Surgery. 1994; 115: 31-38