Prognostic Role of Soluble Urokinase Plasminogen Activator Receptor at the Emergency Department: A Position Paper by the Hellenic Sepsis Study Group.
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SUBMITTER: Velissaris D
PROVIDER: S-EPMC7217599 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Prognostic Role of Soluble Urokinase Plasminogen Activator Receptor at the Emergency Department: A Position Paper by the Hellenic Sepsis Study Group.
Velissaris Dimitrios D Dimopoulos George G Parissis John J Alexiou Zoi Z Antonakos Nikolaos N Babalis Dimitrios D Gerakari Styliani S Kaldis Vassileios V Koutoukas Pantelis P Lada Malvina M Leventogiannis Konstantinos K Pantazopoulos Ioannis I Papadopoulos Antonios A Polyzogopoulou Eftihia E Gogos Charalambos C Armaganidis Apostolos A Giamarellos-Bourboulis Evangelos J EJ
Infectious diseases and therapy 20200512 3
In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of thi ...[more]
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Project description:BackgroundThe biomarker soluble urokinase plasminogen activator receptor (suPAR) is an indicator of inflammation which is increased in a variety of chronic and acute disease states. Its most promising application in the emergency setting is to aid in the prognostic stratification of patients by identifying those at high risk of deterioration. This is a narrative review of studies evaluating the use of suPAR.MethodsWe conducted a Medline search for studies on the use of suPAR in patients acutely admitted to the emergency department.Results25 original studies were included in the review. suPAR as a marker of inflammation has been used alone or combined to other inflammatory biomarkers in the assessment of patients suffering from various acute and chronic diseases in an emergency setting. As it is non-specific, it may increase in infectious disease, malignancy or acute coronary syndromes among other conditions, but quantitative suPAR levels correlate with disease severity. It may be useful for the identification of high risk patients regardless of underlying pathology.ConclusionAs the ideal biomarker in the emergency setting has not been identified yet, suPAR may be a promising addition to the established biomarkers for the initial assessment of patients in this setting. Additional research is necessary to evaluate the usefulness of suPAR guided management algorithms.
| S-EPMC9659827 | biostudies-literature
Project description:ObjectiveUsing biomarkers for early and accurate identification of patients at low risk of serious illness may improve the flow in the emergency department (ED) by classifying these patients as nonurgent or even suitable for discharge. A potential biomarker for this purpose is soluble urokinase plasminogen activator receptor (suPAR). We hypothesized that availability of suPAR might lead to a higher proportion of early discharges.DesignA substudy of the interventional TRIAGE III trial, comparing patients with a valid suPAR measurement at admission to those without. The primary endpoint was the proportion of patients discharged alive from the ED within 24 hours. Secondary outcomes were length of hospital stay, readmissions, and mortality within 30 days.SettingEDs at two university hospitals in the Capital Region of Denmark.Participants16,801 acutely admitted patients were included.Measurements and main resultsThe suPAR level was available in 7,905 patients (suPAR group), but not in 8,896 (control group). The proportion of patients who were discharged within 24 hours of admittance was significantly higher in the suPAR group compared to the control group (50.2% (3,966 patients) vs. 48.6% (4,317 patients), P = 0.04). Furthermore, the mean length of hospital stay in the suPAR group was significantly shorter compared to that in the control group (4.3 days (SD 7.4) vs. 4.6 days (SD 9.4), P = 0.04). In contrast, the readmission rate within 30 days was significantly higher in the suPAR group (10.6% (839 patients) vs. 8.8% (785 patients), P < 0.001). Among patients discharged within 24 hours, there was no significant difference in the readmission rate or mortality within 30 days. Readmission occurred in 8.5% (336 patients) vs. 7.7% (331 patients) (P = 0.18) and mortality in 1.3% (52 patients) vs. 1.8% (77 patients) (P = 0.08) for the suPAR group and control group, respectively.ConclusionThese post hoc analyses demonstrate that the availability of the prognostic biomarker suPAR was associated with a higher proportion of discharge within 24 hours and reduced length of stay, but more readmissions. In patients discharged within 24 hours, there was no difference in readmission or mortality.Trial registration of the main trialThis trial is registered with NCT02643459.
| S-EPMC6545801 | biostudies-literature
Project description:BackgroundSoluble urokinase plasminogen activator receptor (suPAR) has been studied in a variety of diseases. The aim of the study is to investigate the levels of suPAR in neonates with sepsis.MethodsThe infants enrolled to this prospective study were classified into four groups. Group 1, 2, and 3 were referred as the patient groups (40 infants), and group 4 was referred as control group (26 infants). Blood samples for whole blood count, C-reactive protein (CRP), suPAR and blood culture were obtained before initiating antimicrobial therapy, and two further samples were obtained on day 3 and at the end of the treatment for CRP and suPAR.ResultsThe mean gestational ages of patient and control groups was similar. The median level of initial suPAR was 18.8 ng/mL (range 6.8-30.1 ng/mL) in the patient groups, and 6.0 ng/mL (range 3.7-10.8 ng/mL) in the control group (P < 0.001). A significant decrease in suPAR level was observed from the inclusion to the third day and end of the treatment (P < 0.001). The area under the curve (AUC) for suPAR is 0.959 (95% Cl: 0.919-0.999) and for CRP is 0.782 (95% Cl: 0.669-0.895). At a cut-off value of 11.3 ng/mL for suPAR the specificity was 100%, and the sensitivity was 82.5%. There was a positive correlation between laboratory values of CRP and suPAR (r: 0.359, P = 0.003).ConclusionThis is the first study that investigated the levels of suPAR in neonates and our results demonstrate that suPAR is a powerful marker of inflammation in infants with sepsis.
| S-EPMC6806707 | biostudies-literature
Project description:IntroductionRisk stratification in the emergency departments (EDs) is in critical need for new applications due to ED overcrowding and hospitalization of older people. We aimed to evaluate the expediency, efficiency and safety of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), as a tool for the risk assessment of patients arriving at the ED.MethodsWe performed a comparative cross-sectional study in 2 emergency departments (EDs), suPAR measurements being incorporated into routine blood sampling in the intervention ED. The primary outcome was the number of discharges from the ED. The importance of the outcomes was examined by appropriate multi- or bivariate analysis.ResultsThe absolute and relative number of discharges were similar between the intervention and control groups [121 (55.3%) vs 62 (55.9%)]. No significant differences between the groups were seen in the length of stays in the ED. Patients with low suPAR values were more likely discharged and patients with high suPAR values more likely admitted to hospital. Two admitted patients with low suPAR values could have been discharged safely.ConclusionThe utilization of suPAR did not increase the risk for neither positive nor negative outcomes. Low suPAR values could be potential in discharging more patients safely. Instead of unselected patient populations, the benefits of suPAR measurements in the ED could emerge in the assessment of a more precisely determined and selected group of patients.
| S-EPMC8918965 | biostudies-literature
Project description:BACKGROUND:The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in severe acute and chronic medical conditions and has been associated with short-term mortality. The role of suPAR in predicting risk of death following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has never been studied. We hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure. METHODS:This retrospective cohort study from a university hospital in the Capital Region of Denmark included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis, who had plasma suPAR measured at the time of admission between November 18th, 2013 to September 30th, 2015 and followed until December 31st, 2015. Primary outcomes were 30- and 90-days all-cause mortality. Association of suPAR and mortality was investigated by Cox regression analyses adjusted for age, sex, CRP values and Charlson comorbidity index. RESULTS:For patients with AECOPD or underlying COPD, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P <?0.0001). Increasing suPAR levels independently predicted 30-day mortality in patients with COPD with a hazard ratio of 2.0 (95% CI 1.7-2.4) but not respiratory failure. CONCLUSIONS:In this large group of acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality. The study supports the value of suPAR as a marker of poor prognosis.
| S-EPMC5963104 | biostudies-literature
Project description:Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.
| S-EPMC7074407 | biostudies-literature
Project description:BackgroundThe soluble urokinase plasminogen activator receptor (suPAR) is related to hepatic inflammation and fibrosis and has been suggested to participate in the development of liver cirrhosis. Therefore, the aim of the current study was to measure the concentration of suPAR in the hepatic vein of cirrhotic patients during a liver vein catheterization to identify a possible hepatic suPAR generation. Furthermore, we explored if suPAR levels were associated with the degree of cirrhosis and liver dysfunction.Methods and patientsWe included 105 cirrhotic patients and 19 liver-healthy controls. Blood was sampled from the hepatic vein and the femoral artery and suPAR was measured by enzyme-linked immunosorbent assay.ResultsWe identified significantly higher median suPAR concentrations among the cirrhotic patients (7.2 ng/ml in the hepatic vein; 6.8 ng/ml in the femoral artery) compared to the controls (2.6 ng/ml, respectively, p-values <0.001). However, the median hepatic suPAR formation was 0.0 ng/ml in both groups. We observed significantly increasing suPAR levels according to higher Child classes (4.5 ng/ml, 6.9 ng/ml and 9.0 ng/ml, Child A, B, C respectively; p-value<0.001), and significantly higher median suPAR concentrations in patients with ascites versus patients without ascites (8.1 ng/ml versus 5.3 ng/ml, respectively, p-value<0.001). suPAR levels were significantly related to bilirubin (r = 0.48, p<0.001), the hepatic venous pressure gradient (r = 0.39, p<0.001), the cardiac index (r = 0.24, p = 0.02) and the plasma volume (r = 0.33, p = 0.001), whereas suPAR levels were significantly inversely related to albumin (r = -0.59, p<0.001), plasma coagulation factors (r-0.39, p<0.001), the mean arterial pressure (r = -0.28, p = 0.004), the systemic vascular resistance (r = 0.26, p = 0.007), the indocyanine green clearance (r = -0.51, p<0,001) and the galactose elimination capacity (r = -0.39, p<0.001).ConclusionWe identified elevated suPAR concentration in cirrhotic patients, which correlated significantly with the degree of cirrhosis and liver failure, but we were not able to demonstrate hepatic suPAR generation per se. This suggests that further investigations of the source of suPAR in cirrhotic patients need to be undertaken.
| S-EPMC6715219 | biostudies-literature
Project description:Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (β=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.
| S-EPMC9683642 | biostudies-literature
Project description:Background and objectivesBlack Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.Design, setting, participants, & measurementsUsing data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.ResultsAt baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02).ConclusionsHigher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.
| S-EPMC6032570 | biostudies-literature
Project description:The soluble urokinase-type plasminogen activator receptor (suPAR) and the urokinase-type plasminogen activator receptor (uPAR) have been proposed as useful biomarkers of tumor progression. Recently, suPAR was associated with chemoresistance in lung cancer. However, its clinical significance in leukemia has not previously been investigated. The present study examined the plasma levels of suPAR and the expression of the uPAR on bone marrow (BM) cells in 86 patients with leukemia at diagnosis prior to chemotherapy and 26 normal subjects (control group). The plasma suPAR levels were measured using ELISA, whilst uPAR expression was assayed by flow cytometry analysis. In addition, cell surface uPAR expression on K562 and multidrug-resistant K562/ADM cell lines was studied by western blotting. On admission and follow-up, the levels of suPAR in patients with leukemia were significantly increased compared with controls. Systemic levels of suPAR were strongly associated with the numbers of white blood cells. A case was defined as uPAR-positive (uPAR+) if >20% of the gated cells expressed uPAR. In comparison with 26 healthy BM samples that were negative for uPAR expression, 48 (55.8%) of the 86 leukemia patients were uPAR+. uPAR expression on the cell surface of multidrug-resistant K562/ADM cells was increased compared with that on K562 cells. In conclusion, plasma suPAR expression may be a useful marker for subtype classification of patients with leukemia and cell surface uPAR may be associated with resistance to chemotherapy or disease progression.
| S-EPMC5494859 | biostudies-other