Association between serum uric acid and SOFA score in subjects affected by severe sepsis

Background: Serum uric acid (SUA) is a normal product of purine metabolism in humans. Uric acid crystals have the capacity to adhere to the surface of epithelial cells and induce an acute inflammatory response, characterized by systemic cytokine production, tumor necrosis factor, and the local expression of chemokines, monocyte chemotactic protein and cyclooxygenase 2 in blood vessels. Moreover, literature reports a relationship between SUA and different cardiovascular risk factors, including hypertension, metabolic syndrome, chronic kidney disease (CKD), as well as with coronary artery disease, peripheral artery disease, electrocardiographic alterations, cerebrovascular disease, atrial fibrillation, and all-cause mortality. With this study we aimed to evaluate the role of SUA in severe sepsis and septic shock. Materials and Methods: in the period between 2014 and 2015 we enrolled all the patients admitted to our Internal Medicine department for severe sepsis or septic shock. For each patent, at the admission in our department, we evaluated age, sex, the most common comorbidities (hypertension, diabetes, active cancer, CHF, COPD) and smoking attitude. Blood gas analysis, SUA and troponin were collected at the admission. SOFA score was calculated for each subject. Days of hospitalization, death or UTI/SUTI transfer were collected as measures of outcome. Informed consent was required to participate to the study. All patients were treated according to current guidelines. All the data were synthesized in an electronic database. Pearsons bivariate correlation was used to explore relationships between variables. Continuous variables were compared with t-test, dichotomous and ordinal variables with chi-squared test. A GLM/univariate model was used to confirm the preliminary observations controlling for covariates. Statistics was performed with SPSS 13.0 for Windows systems. Results: We obtained a final sample of 71 patients. Mean age was 76.82(±15.37) years, males representing 49.3%. Hypertension affected 72.9%, diabetes 28.2%, cancer 25.4%, CHF 43.7%, COPD 12.7% of the enrolled patients. Mean SUA was 6.49(±0.41) mg/dl, mean troponin I was 0.30(±0.81) mg/dl. Mean SOFA score was 4.34(±0.241). Mean hospitalization was 11.65(±0.68) days. Death or UTI/SUTI transfer was observed in 32.4% of the patients. SUA levels resulted statistically associated to both SOFA score (p<0.05) and death or UTI/SUTI transfer (p<0.001) at Pearsons bivariate test. Patients who died or were transferred to UTI/SUTI had higher mean SUA levels (7.68±5.07mg/dl) than patients who survived (5.92±2.24mg/dl; p<0.05). We observed an exponential relationship between SUA levels and SOFA score (r2=0.836; p<0.0001). The GLM/Univariate model, performed adopting SOFA score as main outcome, SUA levels as main predictor, age, sex, hypertension, smoking attitude, diabetes, cancer, chronic heart failure and COPD as covariates confirmed that patients with SUA levels 7.0 mg/dl had significantly (p=0.01) higher SOFA scores (5.134±0.718) than patients with SUA levels between 4.0 and 6.9 mg/dl (3.562±0.857) and SUA levels under 4.0 mg/dl (3.402±0.857). Conclusions: Among septic patients, increased SUA levels seem to be associated to increased complexity: in this study subjects with hyperuricemia have higher SOFA scores independently of age, sex and all the considered comorbidities. Increased SUA levels seem also be associated to higher UTI/SUTI transfer or in-hospital death. These observations require larger studies to confirm and clarify the nature of this association.