A New Biomarker for Intensive Care Unit Patients: suPAR

Research Article

J Dis Markers. 2015; 2(3): 1030.

A New Biomarker for Intensive Care Unit Patients: suPAR

Nazik S¹*, Ulu A¹, Karakoç E², Özcengiz D³, İnal AS¹, Kurtaran B¹, Kömür S¹, Taşova Y¹ and Aksu HSZ¹

¹Department of Infectious Diseases and Clinical Microbiology, Çukurova University, Turkey

²Department of Internal Intensive Care Unit, Çukurova University, Turkey

³Department of Anesthesiology and Reanimation Çukurova University, Turkey

*Corresponding author: Nazik Selçuk, Department of Infectious Diseases and Clinical Microbiology, Çukurova University, Department of Infectious Diseases and Clinical Microbiology Sarıçam/Adana, Turkey

Received: February 21, 2015; Accepted: September 02, 2015; Published: September 05, 2015

Abstract

Objective: The aim of the current study was to demonstrate the relationship between the suPAR, APACHE II, C-reactive protein (CRP), procalcitonin (PCT) values and the mortality rates of patients under follow-up in the intensive care unit who met the SIRS criteria.

Materials and Methods: Patients were selected from the intensive care units for this single-center, prospective study. Inpatientswho had at least two SIRS criteria, were ≥18 years of age, and spent a duration of ≥72 hours in the intensive care unit were included in the study. The lowest/worst APACHE II score in the first 24 hours, as well as the suPAR, CRP, PCT, lactate values on the days 1 and 5were determined.

Results: An evaluation of the ROC curves for the APACHE II score and the suPAR, CRP, PCT and lactate values measured for the patients in intensive care during the first 24 hours indicated that the APACHE II score had the highest AUC (AUC: 0.824), while the next highest AUCs were observed with suPAR1 (AUC: 0.673), PCT1 (AUC: 0.628), lactate1 (AUC: 0.528), CRP1 (AUC: 0.526). An evaluation of the ROC curves for the suPAR, CRP, PCT and lactate values measured on day 5 indicated that the PCT5 value had the highest AUC (AUC: 0.769), while the next highest AUC values were observed with lactate 5 (AUC: 0.733), suPAR5 (AUC: 0.687) and CRP5 (AUC: 0.648).

Conclusion: These findings suggest that suPAR levels can be used to predict mortality on admission day but not for follow up.

Keywords: APACHE II; Mortality; Sepsis; SIRS; suPAR

Introduction

Bacterial infections and sepsis are the most common causes of mortality and morbidity in intensive care units [1,2]. Early detection of progress to sepsis and reducing the mortality rate are highly important for patients in intensive care units (ICU).

Various biomarkers and scoring systems are used to determine the prognosis of patients in intensive care units. Among these, APACHE II (Acute Physiology and Chronic Health Evaluation II), C-reactive protein (CRP), procalcitonin (PCT) and lactate are among the most important biomarkers.

The APACHE II scoring system is the gold standard to evaluate high-risk patients in intensive care units. This system classifies the patients and provides information about their prognosis. However, this method can yield inaccurate results. For instance, the relative APACHE II score of a young patient who has severe sepsis, but no organ failure is calculated as low [3,4].

CRP and PCT are among the common parameters used to monitor patients in critical condition in intensive care units [5]. However, CRP measurement is not ideal for monitoring sepsis; CRP levels are also elevated in postoperative conditions, autoimmune and rheumatologic diseases and non-infectious conditions such as myocardial infarction. On the other hand, PCT is significantly elevated in bacteremia and sepsis. PCT and CRP have low prognostic value in terms of evaluating the expected life span of sepsis patients [6].

Lactate level is another parameter that is important during progression to SIRS and early sepsis. Tissue hypoxia-dependent hyperlactatemia is observed. Given that oxygen transport to cells is decreased after sepsis, it is difficult to interpret lactate levels.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein-derived potential biomarker for infectious diseases [7]. Urokinase-type plasminogen activator receptor (suPAR) is expressed in neutrophils, lymphocytes, monocytes, macrophages, endothelial cells and malignant cells, and is called suPAR [8,9]. Elevated suPAR levels allow for the prediction of mortality in patients with bacteremia, SIRS, sepsis, and septic shock [9-12].

For the successful treatment of sepsis and SIRS, it is necessary to perform the intervention rapidly and in a timely manner. Thus, the aim of the present study was to analyze suPAR, APACHE II, CRP, PCT, lactate levels in intensive care unit patients who complied with the SIRS criteria, and to determine the association of these parameters with mortality.

Materials and Methods

The study was designed as a prospective and single-center study, and was performed at Cukurova University School of Medicine Department of Infectious Diseases and Clinical Microbiology between February 2013 and October 2013.

Informed consent forms were obtained from the patients or their relatives. Ethics approval was obtained from the institutional ethics committee (Date: 14.02.2013, Project title: A NEW BIOMARKER FOR INTENSIVE CARE UNITPATIENTS: suPAR). Twenty-nine patients from the internal intensive care unit and 29 patients from the reanimation unit were included in the study. A survey was created for the patients, and the required information was recorded on the survey form.

Patients who met these three criteria were included in the study. Terminal cancer patients, patients who received massive blood transfusions, and patients with ongoing pregnancy were excluded from the study.

All patients underwent general evaluation (age, gender, diagnosis, and comorbid conditions). Blood biochemistry, whole blood count, and arterial blood gas measurement were performed for all patients. The APACHE II score was calculated within the first 24 hours of admission to the ICU.

The APACHE II score was calculated by evaluating acute physiological score [body temperature, heart rate, mean arterial pressure, respiration rate, oxygenation, arterial pH, sodium, potassium, creatine, hematocrit, leukocyte count, neurological score (15-Glaskow coma scale)], age, and chronic health condition.

To measure suPAR levels on days 1 and 5 in the ICU, 3 cc blood samples were collected from the peripheral vein into EDTAcontaining tubes. Blood samples were centrifuged at 3,000 rpm for 10 minutes, and plasma samples were separated with the help of a Pasteur pipette. Samples were stored at (-) 80°C until the analysis of suPAR levels. Plasma samples were analyzed by a commercial ELISA kit according to the manufacturer’s instructions (Viro Gates A/S, Denmark).

To measure procalcitonin and CRP levels on days 1 and 5 in the ICU, 5 cc blood samples were collected from the peripheral vein into biochemistry tubes. Blood samples were centrifuged at 4,000 rpm for 5 minutes, and immediatelyanalyzed. A chemiluminescent method was used to analyze PCT levels on a SNIBE MAGLUMI 1000 auto analyzer. A nephelometric method was used to analyze CRP levels on a BECKMAN Coulter IMMAGE 800 auto analyzer. PCT values > 0.5 ng/mL, and CRP values > 0.8 mg/dL were considered significant.

To measure lactate levels on days 1 and 5 in ICU, 1 cc blood samples were collected from the artery into a heparin-containing syringe. Blood samples were analyzed in an ABL 800 blood gas analyzer using ion-selective electrode (amperometric) method. Blood samples were collected in the morning between 8:00 am and 10:00 am.

Statistical analysis

SPSS v.15.0 (SPSS Inc, Chicago, Illinois, USA) was used for statistical analysis. Continuous variables were represented with mean and standard deviation. Numbers and percentages were used to express the categorical variables. The Kolmogorov-Smirnov test was used to compare the mean levels of biomarkers on day 1 and day 5. In case of histograms, the non-parametric Wilcoxon rank test was used to evaluate the variables that did not fit a normal distribution. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of suPAR to predict mortality. According to this method, the following criteria should be met for the best test: sensitivity=100%; false negativity=0 (1-Specificity=0); area under the curve (AUC)=1; and diagnostic value of AUC (p value)<0.05. The Youden index, which uses the point with the highest sensitivity and specificity in the ROC curve, was used to determine the cut-off values. To determine the accuracy of the diagnostic test, the sensitivity, specificity, PPV, and NPV values were calculated at a 95% confidence interval, and were presented in a table. P values <0.05 were considered statistically significant.

Findings

Twenty-nine patients (50%) from the internal intensive care unitand 29 patients (50%) from the reanimation unit were included in the study. Twenty-six patients (44.8%) were male and 32 patients (55.2%) were female. The mean age was 57.54±18.15 years. The median APACHE II score (min-max) at the time of admission to intensive care unit were 23 (range: 3-39).

Patients’ co morbid diseases were evaluated in this study. Accordingly, infection was observed in 40 patients (69%), malignancy was observed in 21 patients (36.2%), hypertension was observed in 17 patients (29.3%), kidney failure was observed in 15 patients (25.9%), surgery was observed in 13 patients (22.4%), and trauma was observed in two patients (3.4%).

Patients’ final conditions were evaluated as alive or exitus. Accordingly, 39 patients (67.2%) were exitus. The main clinical features of the patients are shown in Table 1.