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 is directly linked to disease severity, progression, morbidity, and mortality. suPAR can therefore be used to distinguish 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 leads to less unnecessary hospital admissions, fewer readmissions, and a 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.
How to interpret suPAR results
suPAR level < 4 ng/mL
Supports patient discharge
suPAR level > 6 ng/mL
Supports patient hospitalisation
suPAR is a significant independent predictor of mortality in acute medical patients
| n = 4,343 | Patients dead after 30 days | Patients alive after 30 days | PPV/NPV |
|---|---|---|---|
| suPAR ≥6 ng/ml | 133 | 509 | PPV 20.7% |
| suPAR >3 and l | 77 | 1,580 | |
| suPAR ≤3 ng/ml | 14 | 2,030 | NPV 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 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 an extended 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-days 1–4.
Even taking into account other well-known prognostic factors, including sex, age, Charlson score, and CRP, suPAR remains an independent predictor of readmission and mortality within 30 as well as 90-days 2.
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.
- The 30- and 90-day mortality in patients below 70 years old is 1.5% and 2.9%, respectively2.
- In a patient below 70 years 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 70 years 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 a 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 a 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.
Triage: suPAR in a randomized controlled trial
A randomized controlled trial including more than 16.000 acute medical patients showed that patients who had their 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 the 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 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 with suPAR below and 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
