European Journal of Cardiovascular Medicine

Acute pancreatitis (AP) is a condition marked by localized pancreatic inflammation, which may occur with or without dysfunction in other organs. This condition arises due to the activation of pancreatic enzymes triggered by multiple etiologies, leading to self-digestion, edema, hemorrhage, and, in severe cases, necrosis of pancreatic tissue. The predominant etiological factors remain gallstones and excessive alcohol consumption, accounting for approximately 80% of cases. Less frequently, hypertriglyceridemia, adverse drug reactions, pancreatic malignancies, surgical interventions, trauma, autoimmune disorders, as well as endocrine and metabolic abnormalities (such as hypercalcemia, hyperparathyroidism, and diabetic coma) have been implicated in its pathogenesis [1–4].

Diagnosis of AP requires at least two of the following criteria: (1) characteristic abdominal pain, (2) serum amylase or lipase levels elevated to at least three times the upper normal limit, and (3) imaging evidence of pancreatitis using cross-sectional modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) [5-7]. The Revised Atlanta Classification (RAC) categorizes AP into three subtypes based on severity: mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) [8].

Uric acid, the final metabolite of purine degradation in nucleic acids, is primarily eliminated through glomerular filtration, with a minor portion being degraded by hepatic metabolism. Hyperuricemia, characterized by an abnormally elevated serum uric acid concentration, constitutes the underlying pathological mechanism of gout. When uric acid levels exceed normal thresholds, urate crystals may precipitate and deposit in various tissues, including joints, cardiovascular structures, kidneys, and the pancreas. As an endogenous pro-inflammatory signal released from injured cells, elevated serum uric acid can provoke inflammatory responses, frequently manifesting initially as acute joint swelling accompanied by pain and warmth [9].

Emerging evidence suggests that hyperuricemia is not only implicated in gout pathogenesis but is also linked to various inflammatory diseases. Elevated serum uric acid has been associated with hypertension, metabolic syndrome, obesity, prediabetes, type 2 diabetes mellitus, new-onset diabetes, diabetic nephropathy, and hepatic steatosis [10–16]. Furthermore, inflammatory cytokines, including tumor necrosis factor (TNF), play a crucial role in AP pathophysiology, given its strong association with systemic inflammation. Hence, investigating serum uric acid levels in AP may provide valuable insights.

A study published in 2022 identified elevated serum uric acid as an independent risk factor for AP [17]. However, this study did not explore potential associations between uric acid levels and serological markers. Therefore, the present study aims to determine whether serum uric acid concentrations in AP patients differ from those in healthy individuals and to investigate potential correlations between uric acid levels and serological markers associated with AP.

This prospective study included a total of 234 individuals diagnosed with acute pancreatitis (AP). Patients were included in the study based on specific selection criteria. To be eligible, individuals were required to have a confirmed diagnosis of acute pancreatitis, present to the department within 24 hours of symptom onset, and have no history of prior treatment at other healthcare facilities. Exclusion criteria were also established to maintain the integrity of the study. Patients who refused to undergo uric acid measurement and serological assessments within 24 hours of hospital admission, including hypersensitive C-reactive protein (hs-CRP), triglycerides, total cholesterol, and white blood cell count, were not included. Additionally, individuals who were discharged or succumbed to the illness within 24 hours of hospitalization were excluded from the study. Demographic details, such as age and sex, were documented at the time of admission. On the second day of hospitalization, blood samples were collected to evaluate uric acid levels along with hs-CRP, WBC count, albumin, triglycerides, total cholesterol, fasting blood glucose, and serum calcium, with all values being recorded accordingly.

To compare uric acid levels between patients with acute pancreatitis and healthy individuals, 234 individuals who had undergone routine health examinations at the hospital during the same study period were randomly selected. Their age and uric acid concentrations were documented. If higher uric acid levels were observed in AP patients compared to the healthy population, additional analyses were conducted to examine potential associations between uric acid concentration and serological markers, including hs-CRP, WBC count, albumin, triglycerides, total cholesterol, fasting blood glucose, and calcium, in the 234 AP patients. Furthermore, differences in uric acid levels between patients with mild and non-mild forms of pancreatitis were explored

Descriptive data were presented as median (interquartile range) or percentage values. Normality testing was performed for continuous variables. The Mann–Whitney U test was applied for nonparametric data, while categorical variables were analyzed using either the Chi-square test or Fisher’s exact test. Correlations among variables were determined using Pearson correlation analysis or Spearman rank correlation analysis. Statistical analyses were conducted using SPSS version 23.0, with a P-value of <0.05 considered statistically significant.

The clinical characteristics of acute pancreatitis (AP) cases and healthy controls are summarized in Table 1. The distribution of sex was identical between the two groups (male/female: 146/88), with no significant difference observed (p = 1). The median age was comparable between AP cases and controls (51 years vs. 49 years, p = 0.91). However, the serum uric acid concentration was significantly higher in AP cases compared to controls (344.20 µmol/L vs. 290.50 µmol/L, p < 0.01).

Table 1: Clinical profile of AP cases vs healthy controls

The analysis of uric acid levels in relation to the severity of AP (Table 2) revealed no statistically significant difference between mild and non-mild AP cases. Although the median uric acid concentration appeared slightly higher in non-mild AP compared to mild AP (360.00 µmol/L vs. 345.00 µmol/L), the difference was not statistically significant (p = 0.21). Similarly, no significant differences were observed in age or sex distribution between the two severity groups.

Table 2: Analysis of uric acid levelin mild vs non-mild pancreatitis

Correlation analysis between uric acid levels and serum biomarkers (Table 3) demonstrated a significant positive correlation with serum albumin (r = 0.188, p < 0.05), serum calcium (r = 0.16, p < 0.05), triglycerides (r = 0.322, p < 0.01), and WBC count (r = 0.197, p < 0.01). However, the associations between uric acid and FBS, hs-CRP, and total cholesterol did not reach statistical significance (p > 0.05).

Table 3: Correlation analysis between uric acid and serum biomarkers

Hyperlipidemic acute pancreatitis is defined by a serum triglyceride concentration exceeding 11.3 mmol/L [18]. However, the exact pathophysiological mechanisms underlying hyperlipidemic pancreatitis remain unclear, as it is considered a multifactorial disorder influenced by metabolic, genetic, environmental, and patient-specific factors. Additionally, metabolic disorders such as hypercalcemia and hyperparathyroidism have also been implicated in the development of AP [19]. In this study, a weak correlation was observed between serum uric acid and triglyceride levels. Previous research has already established uric acid as a risk factor for AP [17], suggesting its potential involvement in the disease's pathogenesis.

Uric acid, the terminal product of purine metabolism, accumulates when injured cells undergo rapid degradation of their RNA and DNA, leading to increased purine conversion to uric acid. Hyperuricemia is a recognized component of metabolic syndrome, with its prevalence demonstrating an upward trend. As an endogenous pro-inflammatory signal released from damaged cells, elevated serum uric acid can initiate inflammatory responses [19]. Gout, an inflammatory disorder affecting the joints and kidneys, arises due to persistent hyperuricemia and urate crystal deposition. Beyond gout, elevated uric acid levels have been associated with multiple pathological conditions. A recent study [20] indicated that hyperuricemia serves as a predictive marker for an increased risk of extensive perivascular spaces in the midbrain, suggesting its potential role in cerebral small vessel disease. Research by RII Noor et al. [21] demonstrated a significant association between elevated serum uric acid and stroke severity.

The present study found that patients with AP exhibited significantly higher serum uric acid concentrations compared to the control group. The findings indicated a weak linear correlation between serum uric acid and triglyceride concentrations. As discussed earlier, metabolic conditions such as hypercalcemia, hyperparathyroidism, and hyperlipidemia are implicated in the development of AP. Since hyperlipidemia reflects an abnormal metabolism of blood triglycerides, it raises the question of whether dysregulated uric acid metabolism could also contribute to AP. Pro-inflammatory cytokines such as tumor necrosis factor (TNF) play a crucial role in AP pathogenesis, with animal studies demonstrating that TNF inhibition can mitigate pancreatic injury [22,23]. Since uric acid functions as a pro-inflammatory factor, its dysregulation may also trigger inflammatory responses when levels become elevated. Consequently, similar to hyperlipidemia, hyperuricemia may be involved in the pathophysiology of AP. However, when comparing uric acid levels between mild and non-mild AP cases, no statistically significant differences were detected. Therefore, while uric acid may contribute to AP onset, it does not appear to influence disease severity.

Several limitations should be considered. First, serum uric acid levels in the 234 AP patients included in this study were not measured immediately upon admission but rather the following morning, potentially leading to minor discrepancies from levels at disease onset. Second, the study had a relatively small sample size and was conducted at a single center, which may limit the generalizability of the findings. Finally, although efforts were made to minimize dietary and other external influences on uric acid concentrations, complete elimination of these factors was not possible, introducing a potential source of error. Future studies should incorporate larger cohorts and multi-center designs to validate these findings.

In summary, the findings of this study hold substantial clinical relevance. Individuals diagnosed with acute pancreatitis exhibit significantly elevated uric acid levels compared to healthy individuals. However, uric acid levels did not demonstrate any association with the severity of acute pancreatitis. A linear relationship was observed between uric acid concentration and triglyceride levels.

1. Szatmary P, et al. Acute pancreatitis: Diagnosis and treatment. Drugs. 2022; 82(12):1251–1276.
2. Matta B, et al. Worldwide variations in demographics, management, and outcomes of acute pancreatitis. Clin Gastroenterol Hepatol. 2020; 18(7):1567-1575.e2.
3. Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN. American Gastroenterological Association Institute guideline on initial management of acute pancreatitis. Gastroenterology. 2018; 154(4):1096–1101.
4. Gullo L, et al. Acute pancreatitis in five European countries: Etiology and mortality. Pancreas. 2002; 24(3):223–227.
5. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013; 13(4 Suppl 2):e1–15.
6. Li L, Li L. Risk factors for diabetic ketoacidosis in acute pancreatitis patients with type 2 diabetes. BMC Gastroenterol. 2023; 23(1):257.
7. Li J, Chen J, Tang W. The consensus of integrative diagnosis and treatment of acute pancreatitis-2017. J Evid Based Med. 2019; 12(1):76–88.
8. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis–2012: Revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62(1):102–11.
9. Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003; 425(6957):516–21.
10. van der Schaf N, Brahimaj A, Wen KX, Franco OH, Dehghan A. The association between serum uric acid and the incidence of prediabetes and type 2 diabetes mellitus: The Rotterdam Study. PLoS ONE. 2017; 12(6):e0179482.
11. Ali N, et al. Prevalence of hyperuricemia and the relationship between serum uric acid and obesity: A study on Bangladeshi adults. PLoS ONE. 2018; 13(11):e0206850.
12. Jeong J, Suh YJ. Association between serum uric acid and metabolic syndrome in Koreans. J Korean Med Sci. 2019; 34(48):e307.
13. Kosekli MA, et al. The association between serum uric acid to high-density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: The ABUND study. Rev Assoc Med Bras (1992). 2021; 67(4):549–54.
14. Aktas G, et al. Poorly controlled hypertension is associated with elevated serum uric acid to HDL-cholesterol ratio: A cross-sectional cohort study. Postgrad Med. 2022; 134(3):297–302.
15. Balci SB, Atak BM, Duman T, Ozkul FN, Aktas G. A novel marker for prediabetic conditions: Uric acid-to-HDL cholesterol ratio. Bratisl Lek Listy. 2024; 125(3):145–8.
16. Aktas G, et al. Is serum uric acid-to-HDL cholesterol ratio elevation associated with diabetic kidney injury? Postgrad Med. 2023; 135(5):519–23.
17. Su A, et al. Association between baseline uric acid and the risk of acute pancreatitis: A prospective cohort study. Pancreas. 2022; 51(8):966–71.
18. Adiamah A, Psaltis E, Crook M, Lobo DN. A systematic review of the epidemiology, pathophysiology and current management of hyperlipidaemic pancreatitis. Clin Nutr. 2018; 37(6 Pt A):1810–22.
19. Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: Management of acute pancreatitis. Am J Gastroenterol. 2013; 108(9):1400–15.
20. Zhang T, et al. Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from multi-modality medical imaging study based on KaiLuan study (META-KLS). Prog Neuropsychopharmacol Biol Psychiatry. 2024; 133:111000.
21. Noor R, et al. Serum uric acid and serum lipid levels in patients with acute ischemic stroke admitted in Mymensingh Medical College Hospital. Mymensingh Med J. 2024; 33(2):402–10.
22. Kosekli MA, Herek Ö, Ozmen Ö, Sahinduran S. Ameliorative effect of certolizumab on experimentally induced acute necrotic pancreatitis in rats. Rev Assoc Med Bras (1992). 2019; 65(2):204–10.
23. Hughes CB, et al. Anti-TNF alpha therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat. Am J Surg. 1996; 171(2):274–80