Table 2

Studies evaluating the prognostic value of soluble urokinase-type plasminogen activator receptor (suPAR) levels

First author

Type

Pathology

Patients

Period

Main results

Comments


Sidenius, 2000 [33]

Retrospective

HIV

314 adults, samples taken at enrollment

1991 to 1992

Range of suPAR levels 1.15 to 15.60 ng/ml.

Low (< 3.28 ng/ml), medium (3.28-4.19 ng/ml) and high (> 4.19 ng/ml) suPAR levels related to increasing risk of AIDS-related death. Hazard ratio for death was 2.2 for medium suPAR levels (vs low) and 4.7 for high suPAR levels

Samples were not all obtained at enrollment

Eugen-Olsen, 2002 [29]

Retrospective

Mycobacterium tuberculosis

262 adults, samples taken at enrollment in a cohort based on suspicion of active tuberculosis

8 month-follow-up for 101 patients

1996 to1998

Elevated levels in active TB. 1.25 increase in mortality per ng increase in suPAR.

Not all patients were followed-up

Ostrowski, 2005 [30]

Prospective

HIV

59 healthy individuals + 99 HIV patients. Samples taken at study inclusion-median time from first positive HIV antibody test was 8 (5 to 9) years

2000 to 2001

Higher levels predicted increased mortality risk.

suPAR(I-III) and (II-III) are independent predictors of mortality

Measurement of suPAR (I-III),(II-III) and (I) forms

Ostrowski, 2005 [28]

Prospective

Malaria

645 African children with clinical symptoms of malaria: 478 had malaria.14 healthy children as controls. Samples taken at hospital admission.

June to August of 2000 and 2001

Highest concentrations in non-survivors (11) or with complicated malaria. 1 ng/mL increase in suPAR concentration was associated with increased mortality (OR 1.42)

Low platelet count and hemoglobin level, high neutrophil count were independent predictors of high plasma concentration of suPAR

Lawn, 2007 [32]

Prospective

HIV

293 adults.

Samples taken at enrollment for antiretroviral treatment

Sept 2002 to Feb 2005

5 month follow-up after enrollment

Significantly higher suPAR levels in non survivors.

Log10 suPAR strongly associated with death

No discriminatory cut-off point to provide clinically useful information

Yilmaz, 2010 [22]

Retrospective

CCHF

100 adults, samples taken at hospital admission

2006 to 2009

38 months

Cut-off value of 10.6 ng/ml AUC 0.97

Only 5/100 deaths

No comparison with other infections

Kofoed, 2008 [34]

Retrospective sample analysis

Suspected sepsis

64% bacterial infection

151 adults, samples taken at ED admission

12 months

Mortality:

suPAR AUROC 0.80 (sensitivity 89%, specificity 63%, 95% CI 0.69-0.92).

suPAR and age AUROC 0.92 (sensitivity 100%, specificity 78%, 95% CI 0.86-0.97)

PCT and CRP had no prognostic value

Ostergaard, 2004 [24]

Prospective

CNS infection

183 adults.

Samples taken at admission

1988 to 2002

Positive correlation of CSF suPAR levels with prognosis; cut-off 3.1 mcg/l had OR for death of 11.9 (95% CI 1.4-106)

Multivariate analysis was not possible due to small number of deaths

Wittenhagen, 2004 [14]

Multicenter prospective study

S. Pneumonia bacteremia

141 adults. Samples taken at hospital admission

1999 to 2001; 21 months

Higher suPAR levels in patients compared to healthy volunteers (median 5.5, range 2.4 to 21.0 ng/ml). Levels > 10 ng/ml independent predictor of mortality

(OR 13, specificity 95%, sensitivity 38%, NPV 88%, PPV 60%)

Logistic multivariate regression analysis

Huttunen, 2011 [8]

Prospective cohort study

Bacteremia

132 adults.

Samples taken at day 1 after the first positive blood culture

June 1999 to Feb 2004

11 ng/ml AUROC 0.84 (95% CI 0.76 to 0.93, sensitivity 83%, specificity 76%).

Higher levels associated with disease severity.

OR for mortality16.1 (95%CI 4.3 to 59.9-logistic regression analysis)

Plasma samples were not taken at admission

Molkanen, 2011 [36]

Retrospective sample analysis

S. aureus bacteremia

59 adults.

Samples taken on day 3, after positive blood culture

suPAR AUROC for mortality 0.754 (95% CI 0.615 to 0.894, P = 0.003)

CRP AUROC 0.596.

Cut-off 9.25 ng/ml

Plasma samples not taken at admission

Koch, 2011 [26]

Prospective

Critical illness medical ICU

273 adults, 197 septic.

Samples taken at ICU admission

Undefined

Correlation of suPAR levels with APACHE II score (r = 0.345, P < 0.001), SOFA score (r = 0.337, P = 0.004), SAPS II score (r = 0.271, P = 0.004) and the need for VP and MV. Unadjusted OR for mortality 1.07 (95% CI 1.02 to 1.11)

Cut-off value for mortality 8 ng/ml (day 1) to 13 ng/ml (day 3)

AUROC for ICU/overall survival larger (0.68/0.64) than CRP (0.52/0.53), PCT (0.55/0.55) and APACHE II (0.54/0.60), smaller than SAPS2 (0.81/0.74)

Donadello, 2011 [27]

Prospective

Critical illness, medico-surgical ICU

152 adults, 55 septic.

Samples taken at ICU admission

December 2010 to March 2011

Cut-off value 6 ng/ml (sensitivity 63%, specificity 60%). AUROC for mortality 0.71 (95% CI 0.60 to 0.81) in overall population, in septic patients 0.68 (95% CI 0.47 to 0.88)

Preliminary data


AIDS: acquired immunodeficiency syndrome; APACHE II, Acute Physiology And Chronic Health Evaluation II; AUROC, area under the receiver operating characteristic curve; CCHF, Crimean Congo Hemorrhagic Fever; CNS, central nervous system; CRP, C-reactive protein; CSF, cerebrospinal fluid; ED, emergency department; MV, mechanical ventilation; NPV, negative predictive value; PCT, Procalcitonin; PPV, positive predictive value; OR, odds ratio; SAPS, Simplified Acute Physiology Score; SOFA, sequential organ failure assessment; TB, tuberculosis; VP, vasopressors.

Donadello et al. BMC Medicine 2012 10:2   doi:10.1186/1741-7015-10-2

Open Data