Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Added Predictor to Existing Preoperative Risk Assessments.

BACKGROUND: Risk assessment strategies, such as using the American Society of Anesthesiologists (ASA) physical status classification, attempt to identify surgical high-risk patients. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker reflecting overall systemic inflammation and immune activation, and it could potentially improve the identification of high-risk surgical patients. METHODS: We included patients acutely admitted to the emergency department who subsequently underwent surgery within 90 days of admission. Patients were stratified into low-risk or high-risk groups, according to ASA classification (ASAlow: ASA I-II; ASAhigh: ASA III-VI) and suPAR level, measured at admission (suPARhigh above and suPARlow below 5.5 ng/ml), respectively. Pre-specified complications were identified in national registries and electronic medical records. The association between ASA classification, suPAR level, CRP and the rate of postoperative complications was analyzed with logistic regression and Cox regression analyses, estimating odds ratios and hazard ratios (HRs). RESULTS: During 90-day follow-up from surgery, 31 (7.0%) patients died and 158 (35.6%) patients had postoperative complications. After adjusting for age, sex, and ASA classification, the HR for 90-day postoperative mortality was 2.5 (95% CI 1.6-4.0) for every doubling of suPAR level. suPAR was significantly better than CRP at predicting mortality and all complications (P = 0.0036 and P = 0.0041, respectively). Combining ASA classification and suPAR level significantly improved prediction of mortality and the occurrence of a postoperative complication within 90 days after surgery (P < 0.0001). CONCLUSION: Measuring suPAR levels in acutely admitted patients may aid in identifying high-risk patients and improve prediction of postoperative complications.

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III).

BACKGROUND: Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients. METHODS: The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality. RESULTS: The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results. CONCLUSIONS: The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice. TRIAL REGISTRATION: clinicaltrials.gov, NCT02643459 . Registered 31 December 2015.

suPAR is associated with risk of future acute surgery and post-operative mortality in acutely admitted medical patients.

BACKGROUND: Acutely admitted medical patients are often fragile and in risk of future surgery. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is a predictor of readmission and mortality in the acute care setting. We aimed to investigate if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality. METHODS: A retrospective registry-based cohort study of 17,312 patients admitted to an acute medical unit in Denmark, from 18 November 2013 until 30 September 2015. The first admission with available suPAR was defined as the index admission, and patients were followed via national registries until 1 January 2016. The risk of acute surgery during the entire follow-up period as well as the 90-day post-operative mortality risk was modeled by Cox regression analyses adjusted for sex, age, C-reactive protein, and Charlson Comorbidity Index (Charlson Score). RESULTS: Acute surgery was carried out on 2404 patients (13.9%) after a median of 45 days (interquartile range 5-186) following the index admission. Patients receiving acute surgery had higher baseline suPAR compared with patients receiving elective- or no surgery (p < 0.0001). The hazard ratio (HR) for acute surgery was 1.50 (95% confidence interval (CI): 1.42-1.59) for every doubling of the suPAR level in the adjusted Cox regression analysis. Death within 90 days occurred in 439 (18.3%) patients receiving acute surgery, and the adjusted HR for post-operative mortality was 1.73 (95% CI: 1.52-1.95). DISCUSSION: Elevated levels of suPAR in acutely admitted medical patients were independently associated with increased risk of future acute surgery as well as with 90-day post-operative mortality. TRIAL REGISTRATION: This retrospective registry-based cohort study was approved by the Danish Health and Medicines authority (reference no. 3-3013-1061/1). All processing of personal data followed national guidelines, and the project was approved by the Danish Data Protection Agency (reference no. HVH-2014-018, 02767).