Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients

Abstract

IntroductionsuPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR), which is expressed in various immunologically active cells. High suPAR serum concentrations are suggested to reflect the activation of the immune system in circumstances of inflammation and infection, and have been associated with increased mortality in different populations of non-intensive care patients. In this study we sequentially analyzed suPAR serum concentrations within the first week of intensive care in a large cohort of well characterized intensive care unit (ICU) patients, in order to investigate potential regulatory mechanisms and evaluate the prognostic significance in critically ill patients.MethodsA total of 273 patients (197 with sepsis, 76 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU), on Day 3 and Day 7, and compared to 43 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately one year.ResultsUpon admission to the ICU suPAR serum concentrations were elevated in critically ill patients as compared with healthy controls. In sepsis patients suPAR levels were higher than in non-sepsis patients (with or without systemic inflammatory response syndrome (SIRS)). During the first week after admission to the ICU serum suPAR concentrations remained stably elevated. suPAR serum concentrations measured upon admission were closely and independently correlated to various laboratory parameters, specifically biomarkers of inflammation (tumor necrosis factor (TNF), C-reactive protein (CRP)), hepatic and renal dysfunction. High suPAR levels at admission and at Day 3 were a strong independent predictor for both ICU and long-term mortality in critically ill patients.ConclusionsIn sepsis and non-sepsis patients suPAR serum concentrations are increased upon admission to the ICU, likely reflecting the activation state of the immune system, and remain stably elevated in the initial course of treatment. Low suPAR levels are a positive predictor of ICU- and overall survival in critically ill patients, including sepsis and non-sepsis patients. Aside from its value as a promising new prognostic biomarker, both experimental and clinical studies are required in order to understand the specific effects and regulatory mechanisms of suPAR in SIRS and sepsis, and may reveal new therapeutic options.

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients

“…The ROC-AUC for mortality of suPAR was comparable to previous investigations in ventilated critically ill patients, which could have included many patients with ARDS [6][7][8]. However, the ROC-AUC was low, which could at least in part be because of the high mortality in these patients.…”

“…However insightful, additional measurement of suPAR over time did not fit within the design of this study, aimed at maximum relevancy for use in clinical practice. Furthermore previous research has demonstrated suPAR levels to be stably elevated during the entire first week on the ICU [6]. Finally, combining suPAR with clinical severity scores did not improve the ROC-AUC, yet many other biological markers have been reported as possibly useful in the prediction of mortality in ARDS.…”

“…suPAR is an emerging biomarker in sepsis research. Previous studies in critically ill patients with sepsis or bacteremia have shown a strong association between increasing levels of plasma suPAR and mortality [6][7][8].…”

Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia

“…Additionally, expression and release of uPAR is upregulated by a number of proangiogenic or proatherogenic growth factors, cytokines such as IL-1, and vascular endothelial growth factor, suggesting its involvement in proliferative and inflammatory processes (23). Koch et al demonstrated the prognostic impact of serum suPAR levels during the clinical course within the first week in a large cohort of critical adult patients in a medical intensive care unit (24). Sarafidis et al showed that infants with BPD have an early persistent inflammatory response (25).…”

Circulating suPAR in Two Cohorts of Primary FSGS

“…In most cases in which suPAR is proposed as a marker of inflammation, CRP and suPAR are positively correlated with each other. 13,14 In parallel with the suPAR measurements, serum CRP was determined to assess the inflammatory status in a randomly selected subset of patients from both the FSGS CT and PodoNet cohorts as well as in controls. The average CRP levels were generally low, indicating minimal inflammation, and there was no difference between controls and FSGS patients (Figure 2A).…”