Wed Jun 23 2021

Biomarkers for Sepsis: An Overview

Sepsis is a state of serious infection caused by an unusual response of the body’s immune system to an otherwise ordinary infection1. In general, when the human body is invaded by an infectious agent, the body’s immune system has an inflammatory response. However, in patients with sepsis, the body’s immune system has a hyper-inflammatory response to an infectious agent. Following this abnormal inflammatory response, the body’s immune system goes into an immunosuppressive phase (weak immune system) where multiple organ dysfunction is present. Sepsis is a morbid state where the patient is prone to other types of infectious agents due to a weakened immune system1.
Severe sepsis and associated septic shock are a leading cause of mortality in critically ill patients. Sepsis accounts for an estimated 30-50% of hospital-reported mortality2. Despite various medical interventions, such as antibiotic therapy, extracorporeal membrane oxygenation, activated protein C therapy, human recombinant lactoferrin and TLR 4-blocker therapy, sepsis is associated with a poor prognosis and a high mortality rate2.
The life-threatening nature of sepsis emphasizes the urgent need for early and accurate detection of sepsis. Standard microbial cultures used for the diagnosis of sepsis can be time-consuming and do not provide definite microbiological diagnosis in about one-third of septic patients2. For this reason, reliable biomarkers can assist in the timely diagnosis of sepsis which can enable prompt treatment in patients.

suPAR as a Biomarker for Sepsis

suPAR is a biologic marker of immunologic activation. In septic patients, the biomarker suPAR can be easily measured in the blood or in other body fluids such as cerebrospinal fluid, bronchial washing fluid, saliva, and urine. Scientific research shows that suPAR levels are significantly higher in patients with sepsis than those without2. Several studies have reported suPAR to be an informative biomarker for the severity of sepsis. suPAR is also believed to have a strong prognostic value in assessing the outcome of septic patients2 . A summary of the most important studies supporting suPAR as a biomarker for sepsis are as follows:

  • In 2012, a systematic review published in Intensive Care Medicine demonstrated that suPAR is superior to other biomarkers, including PCT, CRP, and sTREM-1, for predicting the prognosis of sepsis4.
  • Another study published in 2012 in the BMC Medicine found that suPAR has a high predictive value and can be useful for triaging patients for Intensive Care Unit (ICU) admission. The study reported that high suPAR levels may indicate the need for more intense patient monitoring and treatment5.
  • A systematic review and meta-analysis published in 2019 in the journal Shock reported that suPAR is a feasible biomarker for the timely diagnosis and prognosis of sepsis. The study also found that suPAR exhibits similar sensitivity and higher specificity for sepsis diagnosis that procalcitonin (PCT). As per the study, suPAR can also be used for differentiating sepsis from systemic inflammatory response syndrome (SIRS)6.
  • In 2019, a systematic review and meta-analysis studied the effectiveness of six biomarkers in predicting mortality in adult patients with sepsis. The study, published in the Annals of Intensive Care, found that suPAR can provide beneficial prognostic information in adult patients with sepsis7.
  • A 2016 systematic review and meta-analysis published in Nature found that serum suPAR could be a biomarker for the diagnosis and prognosis of bacterial infection. The study also reported that elevated suPAR levels are significantly associated with a high risk of death8.
  • Another study published in 2016 in The American Journal of Emergency Medicine reported that suPAR levels are substantially increased in septic patients and the use of plasma suPAR levels can enhance the efficiency of sepsis diagnosis9.
  • In 2019, a study published in the International Journal of Clinical and Laboratory Medicine reported that suPAR is actively involved in the pathophysiology of sepsis and can be easily and rapidly measured in an Emergency Department (ED)10.

1. Faix JD. Biomarkers of sepsis. Critical Review Clinical Laboratory Science. 2013; PMID: 23480440.
2. Cho SY, Choi JH. Biomarkers of sepsis. Infection & Chemotherapy. 2014. 46(1): 1-12.
3. Nelson GE, Mave V, Gupta A. Biomarkers for sepsis: A review with special attention to India. Blood Stream Infections. 2014.
4. Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Medicinel. 2012. Vol 38.
5. Donadello et.al. suPAR as a prognostic biomarker in sepsis. BMC Medicine. 2012; 10: 2.
6. Huang et.al. The diagnostic and prognostic value of suPAR in patients with sepsis: A systematic review and meta-analysis. Shock. 2019.
7. Pregernig et.al. Prediction of mortality in adult patients with sepsis using six biomarkers: A systematic review and meta-analysis. Annals of Intensive Care. 2019. Vol 9:125.
8. Ni et.al. Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis. Nature. 2016. Vol 6: 39481.
9. Zeng et.al. Clinical value of soluble urokinase-type plasminogen activator receptor in the diagnosis, prognosis, and therapeutic guidance of sepsis. The American Journal of Emergency Medicine. 2016. Vol 34: Issue 3.
10. Velisarris et.al. The use of soluble urokinase plasminogen activator receptor (suPAR) as a marker of sepsis in the emergency department setting: A current review. International Journal of Clinical and Laboratory Medicine. 2019.

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