suPARnostic

suPAR article published in Journal of Internal Medicine 

suPAR researchers Eugen-Olsen et al. had an article published in Journal of Internal Medicine, Sept. 2010:

Abbreviated title of the paper is “suPAR predicts cancer, cardiovascular disease, diabetes and mortality in the general population”.

A cohort of blood samples from 2602 Danish citizens with follow-up after 13 years show that the consequences of living with elevated levels of low-grade inflammation is increased disease and mortality.

The findings support previous studies, showing that an elevated suPAR level is associated with increased risk and poorer prognosis, and hence the data may rationalize why very high suPAR values in hospital patients with critical illness are associated with complications and even risk of death.

Read more on Pub Med

Hot References with Key Findings

 Our scientific literature exemplifies the 3 key suPAR Facts in a variety of disease conditions and applications. Numbers in the table correspond to cited references below.

SEPSIS

1: ”The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality”
Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, and Eugen-Olsen J (2004).
European Society of Clinical Microbiology and Infectious Diseases, 10, 409-415.

Key Findings:

• suPAR level increased Streptococcus pneumoniae bacteraemia, correlating with disease progression.
• suPAR exhibits high specificity, and therefore can be used as prognostic marker to identify high-risk patients.
• suPAR is significantly associated with mortality.

2: “Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome”
Østergaard C, Benfield T, Lundgren JD, Eugen-Olsen J (2004.
Scand J Infect Dis, 36, 14-9.

Key Findings:

• There is a significant difference in suPAR levels among patient groups with significantly higher CSF suPAR levels in patients with CNS infection and encephalitis than in patients without meningitis.
• Patients with purulent meningitis who died had significantly higher CSF levels of suPAR than patients who survived. 
• CSF suPAR levels are an important predictor for fatal outcome in purulent meningitis.

3:  “Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology”
Kofoed K, Schneider UV, Scheel T, Andersen O, and Eugen-Olsen J, (2006)
Clinical Chemistry, 52, 1284-1293

Key Findings:

• suPAR is a stable molecule in plasma
• suPARnostic® antibodies work well with the xMAP technology.

4: “Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study”
Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K, (2007).
Crit Care. 11: R38

and

“Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor”
Kofoed K, Eugen-Olsen J, Petersen J, Larsen K, and Andersen O, (2008).
Eur J Clin Microbiol Infect Dis

These papers are the key papers that explains why suPAR is superior to PCT and CRP in predicting mortality. suPAR is elevated in patients with life threatening infection while PCT and CRP is elevated by bacterial infection. If a patient e.g. dies of viral meningitis during hospitalization, the individual may have lower PCT and CRP that a person with a non-serious bacterial infection.

Key Findings:

• Procalcitonine (PCT) and C-reactive protein (CRP) are elevated by bacterial infection and hence has diagnostic value.
• Procalcitonine and CRP are elevated by bacterial infection in individuals who do not have a serious condtion or high risk of mortality  
• suPAR has NO diagnostic value in SIRS, it is a true prognostic marker (as shown in Kofoed et al., 2007). 
• CRP and PCT have no prognostic value in SIRS. 
• Other potential SIRS markers were included in the analysis. 
• suPAR values, alone and in combination with other markers have the highest AUC for predicting 30-day and 180-day mortality in a group of ICU patients with diagnosed SIRS. 
• Combining suPAR with age has a higher significant AUC (92%) than scoring systems like SAPS  and SOFA II and could therefore be a useful tool to predict outcome in SIRS patients.

TB

5: “The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau”
Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, Gomes VF, Lisse I, (2002) .
Int J Tuberc Lung Dis, 6, 686-692.

Key Findings:

• suPAR levels were increased in TB-patients
• Pre-treatment suPAR levels were predictive of mortality during 8-month TB treatment 
• 8 months of successful treatment lead to significant decrease in suPAR levels suggesting that suPAR measurement to be a useful tool for monitoring treatment response in TB patients. This has later been confirmed in a large EU funded study (publications in 2009)

6: “Correlates for disease progression and prognosis during concurrent HIV/TB infection”
Djoba-Siawaya JF, Ruhwald M, Eugen-Olsen J, and Walzl G, (2007).
International Society for Infectious Diseases, 11, 289-299.

The review gives insight into biomarkers of HIV/TB prognosis.

7: “High mortality risk among individuals assumed to be TB-negative in Guinea-Bissau can be predicted using a simple test”
Rabna P. Andersen A, Wejse C, Oliviera I, Gomes, VF, Andersen MB,Aaby P, Eugen-Olsen J, (2009) .
TMIH, in press.

Key Findings:

• Post-consultation mortality amongst assumed TB-negative individuals is significantly higher than among the general population.
• A highly significant log linear relationship between high suPAR levels and increase in mortality was demonstrated.
• The serum suPAR level can identify individuals with high risk of post-consultation mortality.

8: Coming Soon 

HIV

9: ”Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection”
Sidenius N, Sier CFM, Ullum H, Pedersen BK, Cozzi LA, Blasi F, and Eugen-Olsen J, (2000).
Blood, 96, 4091-4095.

Key Findings:

• suPAR levels increased in HIV-1, correlating strongly with disease progression.
• suPAR was a stronger predictor of survival than CD4 count and viral load.

10: “Soluble urokinase receptor levels in plasma during 5 years of highly active antiviral therapy in HIV-1–infected patients”
Ostrowski SR, Katzenstein TL, Piironen T, Gerstoft J, Pedersen BK, and Ullum H, (2004).
J Acquir Immune Defic Syndr, 35, 337-342.

Key Findings:

• suPAR levels decrease when treatment-naïve HIV-1 patients are treated with HAART (especially during 1st year of treatment, reaching levels close to that of healthy individuals after ~24 months of HAART treatment).
• Data indicate that suPAR level is linked to inflammation in untreated as well as HAART treated HIV-1–infected patients.

11: ”Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1–infected patients initiating highly active antiviral therapy” 
Ostrowski SR, Katzenstein TL, Pedersen M, Høyer-Hansen G, Gerstoft J, Pedersen BK, and Ullum H (2006).
Scandinavian Journal of Immunology, 63, 478-486

Key Findings:

• suPAR levels are strongly linked to immune activation in HIV.
• suPAR correlated positively with sTNFrII both before and after initiation of HAART in HIV-1 – infected patients.

12:”The prognostic value of the suPARnostic® ELISA in HIV-1–infected individuals is not affected by uPAR promoter polymorphisms”
Sneider UV, Nielsen RL, Pedersen C, and Eugen-Olsen J, (2007).
BMC Infectious Diseases, 7, :I34.

Key Findings:

• suPAR is an independent prognostic marker for mortality in HIV-1 patients who are not on ART treatment.
• The results suggest that patients with suPAR levels at or above 6 ng/ml should be considered for initiation of ART. 
• The value of suPAR levels as a biomarker for survival in HIV patients is not affected by uPAR promoter polymorphisms.

13:“Soluble Urokinase Plasminogen Activator Receptor is a Marker of Dysmetabolism in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy”
Andersen O, Eugen-Olsen J, Kofoed K, Iversen J, Haugaard SB (2008).
J. Med. Virol. 80, 209-216.

Key Findings:

• The study found that patients with a cluster of dysmetabolic features have high levels of plasma suPAR compared to patients without lipodystrophy.
• The strong correlations between plasma suPAR and the number of white blood cells, TNF-a, fat distribution, insulin sensitivity, and measures of lipidemia indicate that suPAR could be a significant link between immune constitution and metabolism in these patients. 
• In addition, the present data found that plasma suPAR is a stronger marker of dysmetabolism than TNF-a and IL-6.

MALARIA

14: “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”

Ostrowski SR, Ullum H, Goka BQ, Høyer- Hansen G, Obeng-Adjei G, Pedersen BK, Akanmori BD, Kurtzhals JAL (2005).
Journal of Infectious Diseases, 191, 1331–41.

Key Findings:

• suPAR levels are increased in conditions with immune activation, and high concentrations of suPAR often predict a poor clinical outcome.
• suPAR levels were higher in patients with malaria compared with those in plasmodium-negative patients and those in healthy children. 
• The highest suPAR levels were found in patients with malaria who died or had complicated malaria. 
• A 1 ng/mL increase in plasma concentration of suPAR was associated with an increased risk of mortality.

15: “Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection”
Perch M, Kofoed P, Fischer TK, Co F, Rombo L, Aaby P, Eugen-Olsen J, (2004).
Parasite Immunol, 26, 207-11.

Key Findings:

• The study demonstrated an important association between suPAR and acute malaria infection in humans.
• suPAR levels are reduced to normal levels when treatment with antibiotics are started.