Severe acute pancreatitis is related to increased early urinary levels of the activation Peptide of pancreatic phospholipase A(2).

Background/Aim: In acute pancreatitis, it is believed that generalized activation of pancreatic zymogens leads to autodigestion of the pancreas and if excessive to systemic organ injury. Under physiological circumstances, secretory phospholipase A2 type I (sPLA2-I) is activated by trypsinogen, but the extent of this activation in acute pancreatitis is unclear. The aim of this study was to assess time course and level of activation of sPLA2-I and trypsinogen in acute pancreatitis, relative to severity. Methods: 246 patients were enrolled into a prospective European multicenter study. 137 patients had mild and 35 had severe acute pancreatitis, and there were 74 control patients. Urinary samples were taken on admission and at 6-hour intervals for 48 h, then every 12 h up to 72 h, and finally daily for at least 5 days for measurement of the activation peptide of sPLA2-I (pro-phosphatase A2; PROP) and trypsinogen activation peptide. Results: The median maximum PROP values were significantly elevated 48 h after symptom onset in patients with severe acute pancreatitis [1.52 (95% CI 0.8–2.9) nmol/l] as compared with patients with mild acute pancreatitis [0.72 (0.55-1) nmol/l, p = 0.002] and controls [0.49 (0.22–1.2) nmol/l, p = 0.001], but not before or after this time point. The best cutoff point for urinary PROP to predict overall severity was > 1 nmol/l ≤ 48 h after symptom onset (negative predictive value = 88%), but the PROP levels failed to predict the development of multi-organ dysfunction. Conclusions: Activation of sPLA2-I is associated with the early pathogenesis of acute pancreatitis, but not in the development of distant organ damage. This observation raises questions as to the theory of generalized zymogen activation being a principle mechanism involved in the pathogenesis of distant organ damage in acute pancreatitis.