Soluble urokinase plasminogen activator receptor (suPAR) predicts critical illness and kidney failure in patients admitted to the intensive care unit

Abstract

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3–14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan–Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20–2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7.

Prediction value of soluble urokinase plasminogen activator receptor (suPAR) in COVID-19 patients – a systematic review and meta-analysis

“…27 were selected for full text review, as displayed in the flowchart in Figure 2. Finally, 15 studies were included in this meta-analysis [10,[15][16][17][22][23][24][25][26][27][28][29][30][31].…”

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

“… 3 , 8 , 18 , 21 In addition, suPAR levels may improve risk stratification of critically ill patients, especially in those with moderate organ dysfunction (SOFA score ≤7). 26 The median SOFA score in our study was ≤7 as well, but we included both critically and non‐critically ill patients.…”

“…suPAR is a key regulator of inflammation and immunity and its levels are higher in patients with known risk factors for severe COVID‐19 3,8,18,21 . In addition, suPAR levels may improve risk stratification of critically ill patients, especially in those with moderate organ dysfunction (SOFA score ≤7) 26 …”

A comparative analysis of serial measurements of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and C-reactive protein in patients with moderate COVID-19: a single center study from India

“…Another observation in our study was that longer the patients were required to stay in the hospital due to their criticality, suPAR level were found to be increase proportionally. Earlier studies have reported the length of hospital stay as a measure of disease severity [30,31].…”