suPAR as a biomarker for infectious diseases
The suPAR level is elevated in patients with infectious diseases compared with healthy individuals. An elevated level is associated with:
- Advanced disease
- Poor prognosis
This applies to various infectious diseases including, but not limited to:
- Hepatitis B12
- Hepatitis C13-14
In general, the suPAR level is elevated in patients with infectious diseases. In all infectious diseases studied, an elevated suPAR level is associated with a poorer prognosis. In infectious diseases the prognostic value of suPAR is strong.
“it is essential to have the help of biomarkers, such as suPAR, which can support the discharge decision”
Juan González del Castillo,
Dr PhD, Hospital Clínico San Carlos, Spain
suPAR News Vol. 1, April 2019
In patients with HIV infection, it was demonstrated that the suPAR level is slightly elevated and increases with the disease stage (WHO criteria). The first study of suPAR in HIV showed that suPAR was at least as strong a prognostic marker of the natural progression of HIV, as CD4 and viral load1. Antiretroviral therapy (ART) causes a decrease in suPAR of about 17%2. However, after five years of treatment, the patients’ suPAR level is still higher than in healthy controls2. Side effects of treatment are associated with higher suPAR levels3. In addition to correlating with virological and immunological effects of the infection, the suPAR level correlates with age, metabolic syndrome, smoking, and low muscle mass4. In HIV patients with ART-induced viral suppression, suPAR is a superior and independent predictor of non-AIDS-related comorbidities (e.g. cardiovascular and renal diseases).
In patients with sepsis5-7, it has been found that the suPAR level is of some diagnostic value, as it increases with the seriousness of sepsis and frequently is above 10 ng/mL in patients with impaired organ function8,9. However, most studies show that CRP and procalcitonin (PCT) are better diagnostic markers of bacterial sepsis, whereas suPAR is the best prognostic marker6,10. In a later cohort, it was validated that suPAR in combination with the APACHE score can improve risk stratification of patients with sepsis11.
The suPAR level is elevated in hepatitis B patients with hepatic fibrosis compared to patients with no or mild fibrosis. Thus, suPAR may be useful for identification of hepatitis B patients with significant fibrosis12.
In hepatitis C patients the suPAR level is elevated, and the level increases with the severity of fibrosis. Because hepatic disease and fibrosis affect the suPAR level, the prognostic value and the reflection of disease severity are probably a result of the liver condition rather than the hepatitis C infection13. This is supported by data demonstrating that suPAR is also associated with seriousness and prognosis in patients with non-alcoholic fatty liver disease (NASH)14.
Active tuberculosis (TB) causes a substantial increase in the suPAR level, typically to about 6-7 ng/mL – the higher, the worse15,16. A study from Guinea-Bissau has shown that the suPAR level measured upon initiation of treatment for TB is a prognostic marker of mortality during treatment. Measurement of suPAR following one month of treatment demonstrated that the change in suPAR level was also associated with mortality; patients experiencing no decrease – or even an increase – in suPAR level have a poorer prognosis than patients experiencing a decrease following one month of treatment17.
suPAR has been studied in children, adults, and pregnant women with malaria. In children, a doubling of the suPAR level is observed, which decreases back to a normal level following 14 days of effective treatment18. In adult patients with malaria and acute renal damage, suPAR was associated with the severity of the renal damage and was higher in patients who subsequently needed dialysis19. For pregnant women infected with malaria, a high suPAR level is associated with the low birth weight of the baby20.
An elevated suPAR level in the cerebrospinal fluid (CSF) in children and adults with meningitis is associated with increased mortality21,22.
In children with pneumonia, suPAR is associated with the severity of the infection and length of hospital stay23. In adults with sepsis and ventilator-associated pneumonia, the suPAR level is strongly and independently associated with a negative prognosis24.
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10. Giamarellos-Bourboulis EJ, Georgitsi M. Host response biomarker in sepsis: suPAR detection. Methods Mol Biol 2015;1237:241-6. doi: 10.1007/978-1-4939-1776-1_18.:241- 246.
11. Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V et al. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care 2012;16(4):R149.
12. Sevgi DY, Bayraktar B, Gunduz A et al. Serum soluble urokinase-type plasminogen activator receptor and interferon-gamma-induced protein 10 levels correlate with significant fibrosis in chronic hepatitis B. Wien Klin Wochenschr 2015.
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16. Rabna P, Andersen A, Wejse C et al. High mortality risk among individuals assumed to be TB-negative can be predicted using a simple test. Trop Med Int Health 2009;14(9):986-994.
17. Rabna P, Andersen A, Wejse C et al. Utility of the plasma level of suPAR in monitoring risk of mortality during TB treatment. PLoS One 2012;7(8):e43933.
18. Perch M, Kofoed P, Fischer TK et al. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection. Parasite Immunol 2004;26(5):207-211.
19. Plewes K, Royakkers AA, Hanson J et al. Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria. Malar J 2014;13:91. doi: 10.1186/1475-2875-13-91.:91-13.
20. Ostrowski SR, Ullum H, Goka BQ et al. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 2005;191(8):1331-1341.
21. Tzanakaki G, Paparoupa M, Kyprianou M, Barbouni A, Eugen-Olsen J, Kourea- Kremastinou J. Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome. Eur J Clin Microbiol Infect Dis 2012;31(6):1157-1162.
22. Ostergaard C, Benfield T, Lundgren JD, Eugen-Olsen J. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis 2004;36(1):14-19.
23. Wrotek A, Jackowska T. The role of the soluble urokinase plasminogen activator (suPAR) in children with pneumonia. Respir Physiol Neurobiol 2015;209:120-3. doi: 10.1016/j.resp.2014.12.018. Epub;%2015 Jan 17.:120-123.
24. Savva A, Raftogiannis M, Baziaka F et al. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect 2011;63(5):344-350.
25. Oliveira I, Andersen A, Furtado A et al. Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study. BMJ Open 2012;2(6):e001587.