Dataset Information

Can soluble urokinase plasminogen receptor predict outcomes after cardiac surgery?

ABSTRACT:

Objectives

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that has been implicated in several cardiac pathologies and has been shown to be elevated in critically ill populations. We measured plasma suPAR in a cohort of cardiac surgical patients to evaluate its ability to predict prolonged intensive care unit (ICU) and hospital length of stay and development of complications following surgery. We compared suPAR against EuroSCORE II and C-reactive protein (CRP).

Methods

Ninety patients undergoing cardiac surgery were recruited with samples taken preoperatively and on postoperative days 1, 2 and 3. suPAR was measured using enzyme-linked immunosorbent assay. Area under the receiver operator curve (AUROC) was used to test predictive capability of suPAR. Comparison was made with EuroSCORE II and CRP.

Results

suPAR increased over time (P < 0.001) with higher levels in patients requiring prolonged ICU and hospital stay, and prolonged ventilation (P < 0.05). suPAR was predictive for prolonged ICU and hospital stay, and prolonged ventilation at all time points (AUROC 0.66-0.74). Interestingly, this association was also observed preoperatively, with preoperative suPAR predicting prolonged ICU (AUROC 0.66), and hospital stay (AUROC 0.67) and prolonged ventilation (AUROC 0.74). The predictive value of preoperative suPAR compared favourably to EuroSCORE II and CRP.

Conclusions

suPAR increases following cardiac surgery and levels are higher in those who require prolonged ICU stay, prolonged hospital stay and prolonged ventilation. Preoperative suPAR compares favourably to EuroSCORE II and CRP in the prediction of these outcomes. suPAR could be a useful biomarker in predicting outcome following cardiac surgery, helping inform clinical decision-making.

Clinical registration

West of Scotland Research Ethics Committee Reference: 12/WS/0179 (AM01).

SUBMITTER: Schultz-Swarthfigure CT

PROVIDER: S-EPMC8906672 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Can soluble urokinase plasminogen receptor predict outcomes after cardiac surgery?

Schultz-Swarthfigure Chase T CT McCall Philip P Docking Robert R Galley Helen F HF Shelley Benjamin B

Interactive cardiovascular and thoracic surgery 20210101 2

<h4>Objectives</h4>Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that has been implicated in several cardiac pathologies and has been shown to be elevated in critically ill populations. We measured plasma suPAR in a cohort of cardiac surgical patients to evaluate its ability to predict prolonged intensive care unit (ICU) and hospital length of stay and development of complications following surgery. We compared suPAR against EuroSCORE II and C-reactive protein (CRP).<h4 ...[more]

PMID: 33236082

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Project description:Background and objectivesSoluble urokinase plasminogen activator receptor is a novel biomarker strongly predictive of cardiovascular outcomes implicated in the pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor levels, however, correlate with declining kidney function. It is unclear whether soluble urokinase plasminogen activator receptor levels remain associated with outcomes in patients with ESRD.Design, setting, participants, & measurementsWe measured plasma soluble urokinase plasminogen activator receptor levels in 1175 patients (mean age =66±8 years old, 54% men) with type 2 diabetes mellitus on hemodialysis participating in the German Diabetes and Dialysis Study followed for a median of 4 years for outcomes including all-cause death, cardiovascular events, and infection-related mortality. Survival analysis was performed using stepwise Cox proportional hazards models adjusted for potential confounders. Also, adjustments were made for inflammatory markers (C-reactive protein and leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to investigate potential mediators of the relationship between soluble urokinase plasminogen activator receptor and outcomes.ResultsMedian soluble urokinase plasminogen activator receptor levels were 10,521 pg/ml (interquartile range, 9105-12,543 pg/ml). When stratified by tertiles, patients with soluble urokinase plasminogen activator receptor >11,633 pg/ml (third tertile) had adjusted 1.6-fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03) compared with those with low soluble urokinase plasminogen activator receptor <9599 pg/ml (first tertile). Risks of sudden death and stroke were higher (adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively), together accounting for higher incidence of cardiovascular events (adjusted hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with outcomes persisted after adjusting for C-reactive protein, leukocyte count, and asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator receptor to a risk factor model modestly improved risk discrimination for all-cause death (?C statistic, 0.02; 95% confidence interval, 0.00 to 0.03) and cardiovascular events (?C statistic, 0.02; 95% confidence interval, 0.00 to 0.05).ConclusionsThe association of soluble urokinase plasminogen activator receptor levels with outcomes persists in patients on hemodialysis. Additional study is warranted to characterize the underlying pathways of that association, which may yield opportunities to develop new therapeutic strategies.

Project description:Background & Aims:Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. Methods:Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. Results:High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. Conclusion:Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. Lay summary:Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

Project description:BackgroundThe soluble urokinase plasminogen activator receptor (suPAR) is related to hepatic inflammation and fibrosis and has been suggested to participate in the development of liver cirrhosis. Therefore, the aim of the current study was to measure the concentration of suPAR in the hepatic vein of cirrhotic patients during a liver vein catheterization to identify a possible hepatic suPAR generation. Furthermore, we explored if suPAR levels were associated with the degree of cirrhosis and liver dysfunction.Methods and patientsWe included 105 cirrhotic patients and 19 liver-healthy controls. Blood was sampled from the hepatic vein and the femoral artery and suPAR was measured by enzyme-linked immunosorbent assay.ResultsWe identified significantly higher median suPAR concentrations among the cirrhotic patients (7.2 ng/ml in the hepatic vein; 6.8 ng/ml in the femoral artery) compared to the controls (2.6 ng/ml, respectively, p-values <0.001). However, the median hepatic suPAR formation was 0.0 ng/ml in both groups. We observed significantly increasing suPAR levels according to higher Child classes (4.5 ng/ml, 6.9 ng/ml and 9.0 ng/ml, Child A, B, C respectively; p-value<0.001), and significantly higher median suPAR concentrations in patients with ascites versus patients without ascites (8.1 ng/ml versus 5.3 ng/ml, respectively, p-value<0.001). suPAR levels were significantly related to bilirubin (r = 0.48, p<0.001), the hepatic venous pressure gradient (r = 0.39, p<0.001), the cardiac index (r = 0.24, p = 0.02) and the plasma volume (r = 0.33, p = 0.001), whereas suPAR levels were significantly inversely related to albumin (r = -0.59, p<0.001), plasma coagulation factors (r-0.39, p<0.001), the mean arterial pressure (r = -0.28, p = 0.004), the systemic vascular resistance (r = 0.26, p = 0.007), the indocyanine green clearance (r = -0.51, p<0,001) and the galactose elimination capacity (r = -0.39, p<0.001).ConclusionWe identified elevated suPAR concentration in cirrhotic patients, which correlated significantly with the degree of cirrhosis and liver failure, but we were not able to demonstrate hepatic suPAR generation per se. This suggests that further investigations of the source of suPAR in cirrhotic patients need to be undertaken.

Dataset Information

Can soluble urokinase plasminogen receptor predict outcomes after cardiac surgery?

Objectives

Methods

Results

Conclusions

Clinical registration

Publications

Can soluble urokinase plasminogen receptor predict outcomes after cardiac surgery?

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