Introduction
Materials and methods
Study design and patient characteristics
Parameter | All patients | Sepsis | Non-sepsis |
---|---|---|---|
Number | 273 | 197 | 76 |
Sex (male/female) | 172/101 | 128/69 | 44/32 |
Age median (range) (years) | 64 (18 to 90) | 65 (20 to 90) | 60 (18 to 85) |
APACHE-II score median (range) | 17 (0 to 40) | 18 (0 to 40) | 15 (0 to 31) |
SOFA score median (range) | 11 (0 to 17) | 11 (2 to 17) | 7 (0 to 16) |
SAPS2 score median (range) | 44 (0 to 80) | 44.5 (0 to 79) | 41.5 (13 to 80) |
ICU days median (range) | 9 (0 to 137) | 12 ** (0 to 137) | 6 ** (1 to 45) |
Hospital days median (range) | 27 (2 to 151) | 30 ** (2 to 151) | 14 ** (2 to 85) |
Death during ICU n (%) | 75 (32.8%) | 60 (35.9%) | 15 (24.2%) |
Death during follow-up n (%) | 111 (51.9%) | 83 (53.5%) | 28 (47.5%) |
Mechanical ventilation n (%) | 194 (73.2%) | 144 (75%) | 50 (68.5%) |
Ventilation time median (range) (h) | 126 (0 to 2,966) | 180 * (0 to 2,966) | 48.5 * (0 to 986) |
pre-existing diabetes n (%) | 87 (32.7%) | 59 (30.7%) | 28 (37.8%) |
BMI median (range) (m2/kg) | 25.8 (14.0 to 66.7) | 25.9 (14.0 to 66.7) | 25.8 (15.9 to 53.3) |
suPAR Day 1 median (range) (ng/mL) | 9.80 (0 to 20) | 11.05 ** (1.87 to 20) | 7.62 ** (0 to 20) |
suPAR Day 3 median (range) (ng/mL) | 10.83 (2.33 to 20) | 12.11 * (2.59 to 20) | 8.47 * (2.33 to 20) |
suPAR Day 7 median (range) (ng/mL) | 11.90 (3.67 to 20) | 12.27 (3.94 to 20) | 9.73 (3.67 to 20) |
Characteristics of sepsis and non-sepsis patients
Sepsis | Non-sepsis | ||
---|---|---|---|
n = 197 | n = 76 | ||
Etiology of sepsis critical illness
| |||
Site of infection | n (%) | ||
Pulmonary | 116 (59%) | ||
non-pulmonary | 81 (41%) | ||
Etiology of non-sepsis critical illness
| |||
n (%) | |||
decompensated liver cirrhosis | 19 (25%) | ||
non-sepsis other | 57 (75%) |
suPAR measurements
Statistical analysis
Results
suPAR serum concentrations upon admission to the ICU are elevated in critically ill patients as compared with healthy controls and are higher in sepsis than in non-sepsis patients
suPAR serum concentrations remain stably elevated during the clinical course within the first week after ICU admission
suPAR serum concentrations at admission to the ICU are closely correlated to biomarkers of inflammation, organ function and clinical scores
All patients | Sepsis | Non-sepsis | ||||
---|---|---|---|---|---|---|
Parameters |
r |
P
|
r |
P
|
r |
P
|
Markers of inflammation
| ||||||
TNF-α | 0.571 | < 0.001 | 0.555 | < 0.001 | 0.583 | 0.001 |
CRP | 0.411 | < 0.001 | 0.408 | < 0.001 | - | n.s. |
Procalcitonin | 0.468 | < 0.001 | 0.437 | < 0.001 | 0.418 | 0.003 |
Markers of organ function
| ||||||
Creatinine | 0.352 | < 0.001 | 0.273 | < 0.001 | 0.430 | < 0.001 |
Urea | 0.400 | < 0.001 | 0.326 | <0.001 | 0.458 | < 0.001 |
Cystatin C | 0.638 | < 0.001 | 0.557 | < 0.001 | 0.724 | < 0.001 |
Cystatin C GFR | -0.649 | < 0.001 | -0.583 | < 0.001 | -0.714 | < 0.001 |
Bilirubin | 0.243 | < 0.001 | 0.194 | 0.012 | 0.413 | < 0.001 |
yGT | 0.354 | < 0.001 | 0.350 | < 0.001 | 0.367 | 0.002 |
AP | 0.441 | < 0.001 | 0.379 | < 0.001 | 0.599 | < 0.001 |
PCHE | -0.492 | < 0.001 | -0.449 | < 0.001 | -0.438 | < 0.001 |
Albumin | -0.444 | < 0.001 | -0.387 | < 0.001 | -0.430 | 0.003 |
INR | 0.300 | < 0.001 | 0.214 | 0.006 | 0.416 | < 0.001 |
ATIII | -0.416 | < 0.001 | -0.300 | 0.006 | -0.507 | 0.002 |
IGF-1 | -0.379 | < 0.001 | -0.247 | 0.029 | -0.625 | < 0.001 |
Base excess | -0.217 | 0.001 | -0.291 | < 0.001 | - | n.s. |
ICU treatment measures
| ||||||
FiO2 | 0.230 | 0.043 | - | n.s. | - | n.s. |
PEEP | 0.319 | 0.004 | 0.265 | 0.042 | - | n.s. |
Norephinephrine dose | 0.131 | 0.050 | 0.202 | 0.011 | - | n.s. |
Clinical scoring
| ||||||
APACHE II | 0.345 | < 0.001 | 0.353 | < 0.001 | - | n.s. |
SOFA | 0.337 | 0.004 | - | n.s. | - | n.s. |
SAPS2 | 0.271 | 0.004 | 0.346 | 0.002 | - | n.s. |
suPAR is a strong predictive marker for ICU- and overall survival in critically ill patients
Admission | Day 3 | Day 7 | |
---|---|---|---|
Survivor ICU | n = 180 | n = 135 | n = 87 |
suPAR median (range)(ng/mL) | 9.47 (0 to 20) | 10.07 (2.3 to 20) | 10.93 (3.6 to 20) |
Death ICU
| n = 61 | n = 51 | n = 34 |
suPAR median (range) (ng/mL) | 11.73 (3.4 to 20) | 14.01 (3.2 to 20) | 14.46 (5.6 to 20) |
Survivor overall
| n = 116 | n = 95 | n = 58 |
suPAR median (range) (ng/mL) | 7.98 (2.31 to 20) | 9.84 (2.33 to 20) | 10.66 (3.67 to 20) |
Death overall
| n = 115 | n = 85 | n = 60 |
suPAR median (range) (ng/mL) | 11.25 (0 to 20) | 12.10 (3.10 to 20) | 12.75 (5.38 to 20) |
Parameter | Unadjusted HR (95% CI) |
P-value
| Adjusted HR (95% CI) |
P-value
|
---|---|---|---|---|
C-reactive protein | - |
n.s.
| - |
n.s.
|
procalcitonin | - |
n.s.
| - |
n.s.
|
albumin | 0.940 (0.907 to 0.973) |
< 0.001
| 0.926 (0.885 to 0.969) |
0.001
|
INR | 1.723 (1.302 to 2.28) |
< 0.001
| - |
n.s.
|
creatinine | - |
n.s.
| - |
n.s.
|
suPAR | 1.067 (1.022 to 1.113) |
0.003
| 1.089 (1.027 to 1.154) |
0.004
|
suPAR has superior prognostic value as compared with single parameters of inflammation and organ dysfunction in critically ill patients
Discussion
Conclusions
Key messages
-
Soluble urokinase plasminogen activator receptor (suPAR) is derived from various immunologically active cells and suggested to reflect general inflammation and the extent of resulting immune-activation.
-
In critically ill patients suPAR serum concentrations are significantly increased compared to healthy controls, especially in patients with sepsis, and remain stably elevated within the first week of critical disease.
-
suPAR is closely correlated to inflammatory markers indicating substantial involvement in systemic inflammatory response in critical disease.
-
suPAR correlates to renal and liver function indicating possible routes of clearance.
-
suPAR is a strong predictor for ICU and overall survival in critically ill patients.