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suPAR in the Emergency Department

suPAR is a prognostic tool reflecting the extent of activation of our immune system non-specific to any individual disease.

The key advantage of suPAR is that it, across diseases, is directly linked to disease severity and progression, as well as morbidity and mortality and can therefore be used to discriminate between non-survivors and survivors.

In Acute Triage, this will allow the hospital to:

  • Improve patient care by identifying, treating and hospitalizing high-risk patients and identifying those who can be discharged. This in turn leads to less unnecessary hospital admissions, fewer readmissions, and shorter length-of-stay.
  • Reduce healthcare costs by being able to classify more patients into the low-risk category.
  • Empower their clinical staff by being able to make clear triage decisions and reducing doubts and stress.
A drawing of what suPAR is and how it can be used

suPARnostic® Patient Guideline: suPARnostic® improves patient care and reduces healthcare costs by classifying 34% more patients into low-risk category. 8

suPAR is a significant independent predictor of mortality of ED patients

n = 4,343Patients dead after 30 daysPatients alive after 30 daysPPV/NPV
suPAR ≥6 ng/ml133509PPV
20.7%
suPAR >3 and l771,580
suPAR ≤3 ng/ml142,030NPV
99.3%
Sensitivity/Specificity
(suPAR ≤3 versus
≥6 ng/ml)
Sensitivity
90.5%
Specificity
80.0%

Source: Rasmussen LJH, Ladelund S, Haupt TH, et al. Emerg Med J 2016;33:769-775

Studies from various Emergency Departments located in the Copenhagen region, Denmark, have shown that suPAR is associated with:

    • Age1,2
    • Severe and/or multiple comorbidities1,2
    • Length of hospital stay2
    • Admission to an intensive care unit2,3
    • Readmission within 30 and 90 days2
    • 48-hour, 30-day and 90-day mortality2

This means that in acute medical patients, suPAR measured on admission is higher in elderly patients, patients who end up being admitted for a long period, patients ending up in the intensive care unit, seriously or chronically ill patients, and multimorbid patients as well as patients who are readmitted or die within 30 as well as 90 days1–4.

Even taking into account other well-known prognostic factors, including sex, age, Charlson score, and CRP, suPAR still remains an independent predictor of readmission and mortality within 30 as well as 90 days2.

Medical staff discussing over medical reports in hospital

On the other hand, patients with a low suPAR level are at a lower risk of being readmitted or dying compared to others of the same age. Example:

      • The background 30- and 90-day mortality in patients below the age of 70 is 1.5% and 2.9%, respectively2.
      • In a patient below the age of 70 with a suPAR level of 0-3 ng/mL, the risk of dying within 30 and 90 days is 0.3% and 0.8%, respectively2.
      • By comparison, in a patient below the age of 70 with a suPAR level above 9 ng/mL the risk of dying within 30 and 90 days is 19.7% and 27.6%, respectively2.

Data from Hvidovre Hospital Emergency Department2.

Median (25-75%) suPAR level:

  • 0-50 years: 2.3 ng/mL (1.8-3.0)
  • 50-70 years: 3.0 ng/mL (2.3-4.2)
  • >70 years: 4.4 ng/mL (3.2-6.1)

Median suPAR level (25-75%):

  • ÷ intensive care unit: 3.2 ng/mL (2.2-4.6)
  • + intensive care unit: 5.6 ng/mL (3.0-7.9)

Median suPAR level (25-75%):

  • Neither readmission nor mortality within 30 days: 3.0 ng/mL (2.2-4.2)
  • Readmission within 30 days: 3.9 ng/mL (2.7-5.6)

Median suPAR level (25-75%):

  • 0 days: 2.6 ng/mL (1.9-3.6)
  • 2-4 days: 3.7 ng/mL (2.7-5.3)
  • >10 days: 5.1 ng/mL (3.6-7.5)

Median suPAR level (25-75%):

  • No comorbidities: 2.9 ng/mL (2.1-4.2)
  • Charlson score = 1: 3.7 ng/mL (2.7-5.4)
  • Charlson score ≥ 4: 7.2 ng/mL (4.8-10.9)

Median suPAR level (25-75%):

  • Survived for 30 days: 3.1 ng/mL (2.2-4.5)
  • Died within 30 days: 6.8 ng/mL (4.7-9.9)
  • 30-day mortality AUC: 0.84 (95% CI: 0.81-0.86)

suPAR and clinical signs

suPAR is correlated with disease severity, but is suPAR correlated to the clinical signs? In a study published in Critical Care Medicine in 2018, the authors found that suPAR is correlated to the number of clinical signs (registered using the NEWS score) – however, many patients with none or 1 clinical sign had high suPAR (Figure 2) and these patients (as illustrated with the red box) had high risk of mortality5. Interestingly, suPAR was even stronger for those with none or few clinical signs compared to those presenting with multiple clinical signs, perhaps because these patients do not receive the same level of clinical attention5.

Figure 2: suPAR levels accordign to NEWS score.
A table showing the different suPAR categories

suPAR in a randomized controlled trial

An RCT including more than 16.000 acute medical patients showed that patients who had the suPAR level measured (suPAR group) were significantly more often discharged within 24 hours of admittance compared to patients without suPAR levels measured (control group). Furthermore, the mean length of hospital stay in the suPAR group was 6,5 hours shorter compared to control group (p<0.05).6

Although significantly more patients were discharged within 24 hours, there was no increased mortality among these patients. In those who were discharged with suPAR, 30-day mortality was 1,3% and in the control arm it was 1,8% (p=0.08). The suPAR AUC for 30-day mortality among the patients discharged within 24 hours was 0.92.7 Further analysis of the triage data showed that the Youden index was 5,9 ng/ml. Triaging patients down with suPAR below and up above the Youden index (5,9 ng/ml) resulted in 34% more patients triaged green
(Figure 3).

1.Haupt, T. H. et al. Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study. Crit. Care 16, R130 (2012).
2. Rasmussen, L. J. H. et al. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort studyEmerg Med J. 2016 Nov;33(11):769-775
3. Raggam, R. B. et al. Soluble urokinase plasminogen activator receptor predicts mortality in patients with systemic inflammatory response syndrome. J. Intern. Med. 276, 651–8 (2014).
4. Nayak, R. K., Allingstrup, M., Phanareth, K. & Kofoed-enevoldsen, A. suPAR as a biomarker for risk of readmission and mortality in the acute medical setting. 62, 1–4 (2015).
5. Rasmussen LJH et al, Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study. Crit Care Med. 2018 Dec;46(12):1961-1968
6. Schultz M at al. Availability of suPAR in emergency departments may improve risk stratification: a secondary analysis of the TRIAGE III trial. Scand J Trauma Resusc Emerg Med. 2019 Apr 11;27(1):43.Martin Schultz, Line J. H. Rasmussen, Thomas Høi-Hansen, et al., “Early Discharge from the
7. Schultz et al. Emergency Department Based on Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels: A TRIAGE III Substudy,” Disease Markers, vol. 2019, Article ID 3403549, 8 pages, 2019
8. Schultz et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2019, 27:43

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published suPAR studies in leading medical journals

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