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.
Highlights
In comatose non-surviving patients, the local Institutional Review Board (IRB) acted as legal guardian and gave consent for participation within the study
We found that ICU non-survivors had higher levels of Soluble urokinase plasminogen activator receptor (suPAR) and that suPAR was a strong predictor of ICU mortality
We investigated whether suPAR levels on hospital discharge were able to predict unplanned 90-day readmission rate
Summary
The primary objective was to assess the prognostic value of baseline plasma suPAR at ICU admission with regard to ICU- and 28-day mortality. Secondary objectives as prespecified by the study protocol included the association of suPAR with coagulation and inflammatory markers, as well as SOFA score. SuPAR-level differences in prespecified subgroups and the diagnostic value of suPAR with regards to AKI-3 were investigated. All statistical analyses were performed with SPSS 26 (SPSS Inc, Chicago, Illinois, USA) and Stata 15.0 (Stata Corp., Houston, TX, USA). Associations between variables were computed with cross-tabulations, Mann–Whitney-U-tests, χ2-tests, and Fisher’s exact tests, as appropriate. Spearman’s rank-based correlation coefficient was used for correlations analyses. The prognostic associations between 28-day / ICU mortality and other potential baseline predictors were computed with univariable and multivariable logistic regression. Formal adjustment for multiple testing was not performed.
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