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 |