suPAR as a biomarker for infectious diseases
The suPAR level is elevated in patients with infectious diseases compared with healthy individuals, and an elevated level is associated with:
- Advanced disease
- Poor prognosis
This applies to various infectious diseases, among others:
- Hepatitis B12
- Hepatitis C13-14
In general, the suPAR level is slightly elevated in patients with infectious diseases, and in all infectious diseases studied, an elevated suPAR level is associated with a poorer prognosis. In infectious diseases, the diagnostic value of suPAR is weak, but instead it has a prognostic value.
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 5 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 the correlation 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 ARTinduced viral suppression, suPAR is a superior and independent predictor of non-AIDS events 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 seriousness of sepsis and is frequently 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 shown and validated that suPAR in combination with the APACHE score can improve the 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 disease14.
Active tuberculosis (TB) causes a substantial increase in 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.
In malaria, suPAR has been studied in children, adults, and pregnant women. 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 severity of the renal damage and was higher in patients who subsequently needed dialysis19. In pregnant women infected with malaria, a high suPAR level is associated with 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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