Kadir KÜÇÜKCERAN, Mehmet ERGİN, İbrahim KILINÇ, Adnan KARAİBRAHİMOĞLU, Tamer ÇOLAK, Alpay TUNCAR, Zerrin Defne DÜNDAR, Sedat KOÇAK, Abdullah Sadık GİRİŞGİN, Mehmet GÜL, Başar CANDER

The role of soluble urokinase plasminogen activator receptor (SuPAR) as an indicator of the severity of acute pancreatitis

Background/aim: Soluble urokinase plasminogen activator receptor (suPAR) has been reported to have a positive correlation with the activation degree of the immune system. This study's aim is to investigate the efficiency of SuPAR serum levels in acute pancreatitis (AP) patients in determining the severity of disease. Materials and methods: This prospective research involves patients who arrived at the emergency service, were over 18 years old, had nontraumatic abdominal pain and diagnosis of AP, and agreed to join the study. Demographic characteristics, contact information, laboratory and imaging test parameters, Ranson's criteria, the Balthazar Severity Index, the Rapid Acute Physiologic Score (RAPS), and the modified Glasgow (Imrie) score of all patients were recorded. Two study groups were created as score of <3 (mild, Group I) and ≥3 (severe, Group II) for pancreatitis according to Ranson's criteria. Results: During the study period, 59 sequential patients with AP were included in the study. It was seen that 79.7% of the study group (n = 47) were in Group I. Etiologically 67.8% (n = 40) cases were biliary and 32.3% (n = 19) were nonbiliary diseases. According to the results, suPAR level was effective in distinguishing the severity of AP (AUC = 0.902, P < 0.001 (95% CI: 0.821-0.984)). With regard to determining severe disease, suPAR had an optimum cutoff value of 6.815 ng/mL, sensitivity of 91.66%, specificity of 82.97%, and negative predictive value of 97.5%. Conclusion: Our study was performed the determine the efficiency of suPAR level in predicting severe disease in AP patients. We found it significant in indicating the severity of disease according to the study results.

Keywords:

Acute pancreatitis, biomarker, abdominal pain, suPAR,

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Anirban M. Pancreas. In: Kumar V, Abbas AK, Aster JC, editors. Robbins Basic Pathology. 10th ed. Philadelphia, PA, USA: Elsevier; 2017. pp. 679-691.
Bradley EL 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, GA, September 11 through 13, 1992. Arch Surg 1993; 128: 586-590.
Sarr MG, Nagorney DM, Mucha P Jr, Farnell MB, Johnson CD. Acute necrotizing pancreatitis: management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. Br J Surg 1991; 78: 576- 581.
Beyazıt Y, Önal İK, Kurt M, Kekilli M, Taş A, Pürnak T, Sayılır A, Yeşil Y, Arhan M, İbiş M. Akut pankreatitde prognozu ve hastanede yatış süresini etkileyen faktörlerin değerlendirilmesi. Yeni Tıp Dergisi 2011; 28: 43-46 (in Turkish).
Hirota M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, Sekimoto M, Kimura Y, Takeda K, Isaji S et al. JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 33-41.
Juffermans NP, Dekkers PE, Verbon A, Speelman P, van Deventer SJ, van der Poll T. Concurrent up regulation of urokinase plasminogen activator receptor and CD11b during tuberculosis and experimental endotoxemia. Infect Immun 2001; 69: 5182-5185.
Backes Y, Van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med 2012; 38: 1418-1428.
Suberviola B, Castellanos-Ortega A, Ruiz Ruiz A, Lopez-Hoyos M, Santibañez M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission. Intensive Care Med 2013; 39: 1945-1952.
Sargent S. Pathophysiology, diagnosis and management of acute pancreatitis. Br J Nurs 2006; 15: 999-1005.
Mitchell RM, Byrne MF, Baillie J. Pancreatitis. Lancet 2003; 361: 1447-1455.
Sanfley H, Bulkley GB, Cameron JL. The role of oxygen- derived free radicals in the pathogenesis of acute pancreatitis. Ann Surg 1984; 200: 405-413.
Dobrowski A, Gabryelewicz A, Wereszczyńska-Siemiatkowska U, Chyczewski L. Oxygen derived free radicals in cerulean- induced Acute Pancreatitis. Scand J Gastroenterol 1988; 47: 1245-1249.
Yilmaz G, Köksal I, Karahan SC, Mentese A. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome. Clin Biochem 2011; 44: 1227-1230.
Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 2000; 12: 613–620.
Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers 2009; 27: 157–172.
Alhajeri A, Erwin S. Acute pancreatitis: value and impact of CT severity index. Abdom Imaging 2008; 33: 18-20.
De Bernardinis M, Violi V, Roncoroni L, Boselli AS, Giunta A, Peracchia A. Discriminant power and information content of Ranson’s prognostic signs in acute pancreatitis: a meta-analytic study. Crit Care Med 1999; 27: 2272
Bollen TL, van Santvoort HC, Besselink MG, van Leeuwen MS, Horvath KD, Freeny PC, Gooszen HG; Dutch Acute Pancreatitis Study Group. The Atlanta Classification of acute pancreatitis revisited. Br J Surg 2008; 95: 6-21.
Zeytunlu M, Akyıldız A, Tekeşin O, Ersöz G, Özütemiz Ö, Çoker A, Yüzer Y, Batur Y. Akut pankreatit olgularının kanıta dayalı tıp kılavuzları rehberliğinde incelenmesi. Akademik Gastroenteroloji Dergisi 2005; 4: 146-153 (in Turkish).
Aygencel G, Karakan T, Türkoğlu MA. Akut pankreatit tanısıyla yatan hastaların analizi. MN Dahili Tıp Bilimleri 2009; 4: 131- 139 (Turkish).
Tasić T, Grgov S, Nagorni A, Benedeto-Stojanov D. Comparison of biohumoral and morphological parameters in acute pancreatitis. Srp Arh Celok Lek 2014; 142: 29-33.
Visser RJ, Abu-Laban RB. Acute and chronic pancreatitis. In: Tintinalli JE, Kelen GD, Stapczynski JS, editors. Emergency Medicine A Comprehensive Study Guide. 5th ed. New York, NY, USA: McGraw-Hill; 2000. pp. 588-592.
Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, Eugen-Olsen J. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 2004; 10: 409-415.
Koch A, Voigt S, Kruschinski C, Sanson E, Dückers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F. Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Critical Care 2011; 15: R63.
Hoenigl M, Raggam RB, Wagner J, Valentin T, Leitner E, Seeber K, Zollner-Schwetz I, Krammer W, Prüller F, Grisold AJ et al. Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome. Clin Biochem 2013; 46: 225-229.
Yilmaz G, Mentese A, Kaya S, Uzun A, Karahan SC, Koksal I. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol 2011; 50: 209-211.
Ostergaard C, Benfield T, Lundgren JD, Eugen-Olsen J. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis 2004; 36: 14-19.
Kofoed K, Eugen-Olsen J, Petersen J, Larsen K, Andersen O. Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor. Eur J Clin Microbiol Infect Dis 2008; 27: 375-383.
Savva A, Raftogiannis M, Baziaka F, Routsi C, Antonopoulou A, Koutoukas P, Tsaganos T, Kotanidou A, Apostolidou E, Giamarellos-Bourboulis EJ et al. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect 2011; 63: 344-350.
Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, Gomes VF, Lisse I. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea- Bissau. Int J Tuberc Lung Dis 2002; 6: 686-692.
Ostrowski SR, Ullum H, Goka BQ, Høyer-Hansen G, Obeng- Adjei G, Pedersen BK, Akanmori BD, Kurtzhals JA. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 2005; 191: 1331-1341.
Seppala RU, Huttunen R, Tarkka M, Aittoniemi J, Koskinen P, Leino A, Vahlberg T, Rintala EM. Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study. J Intern Med 2012; 272: 247-256.
Nikkola A, Aittoniemi J, Huttunen R, Rajala L, Nordback I, Sand J, Laukkarinen J. Plasma level of soluble urokinase-type plasminogen activator receptor predicts the severity of acute alcohol pancreatitis. Pancreas 2017; 46: 77-82.
Lipinksi M, Rydzewska-Rosolowska A, Rydzewska A, Cicha M, Rrdzewska G. Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity. Pancreatology 2017; 17: 24-29.