suPAR in Surgery
A high preoperative suPAR level is associated with:
- Post-operative complications
- Increased mortality risk3
- Poor prognosis5,6,8-10
- Postoperative pneumonia7
- Prosthetic joint infection11
suPAR is a well-studied biomarker predicting prognosis, disease severity, and organ dysfunction and is being considered as a marker of the individual’s inflammatory status. It has been demonstrated that biomarkers are able to improve triage and are effective in identifying high and low risk patients among acutely admitted patients1. Improving the preoperative risk stratification using biomarkers may optimize the patient‘s clinical outcome2. Available data on use of biomarkers in addition to risk stratification are observational data, and suPAR has mainly been studied in medical and oncological patients.
Gastric surgery patients and orthopedic surgery patients were included in a study conducted in the emergency department at Hillerød Hospital, Denmark. The TRIAGE study included 5992 unselected patients and confirmed the prognostic value of suPAR regarding mortality, and found it similar in both medical and surgical patients. In the same study, it was shown that triage based on suPAR level was superior to the current triage system in predicting 30-day mortality: AUC 0.84 (0.82-0.87) vs. 0.62 (0.58-0.66), respectively. In multivariate analyses of 30-day mortality in relation to suPAR quartiles, adjusted for sex, age, CRP, leucocytes, and triage category, HR was 1.0, 2.2, 8.3, and 26.9 in the upper quartile3. Of the acute medical patients, 697 had a surgical intervention registered within 3 months after admission. 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)12.
“It has become clear that suPAR is a very strong prognostic marker, exceeding the prognostic value of all other routinely measured biomarkers in our hospital.”
Prof. Ove Andersen,
MD, PhD, DmSc, Copenhagen University Hospital Hvidovre, Denmark
suPAR News Vol. 3, June 2020
In acute medical patients, elevated suPAR is associated with increased risk of acute surgery
Acutely admitted medical patients are often fragile and in risk of future surgery. A Danish group investigated if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality13. In a retrospective registry-based cohort study of 17,312 patients, acute surgery was carried out on 2404 patients (13.9%) after a median of 45 days (IQR 5-186) following the index admission. Patients receiving acute surgery had higher baseline suPAR compared with patients receiving electiveor 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). The authors conclude that 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 mortality13.
A high suPAR level has been demonstrated in both tumor tissue and in blood, and in several cancers, the suPAR level is shown to correlate with a poor prognosis4. In a few studies, suPAR has been studied as a potential biomarker in gastric surgery.
In a cohort of 518 elective colorectal cancer patients, preoperative measurement of the suPAR level was performed. In multivariate analyses adjusted for age, sex, tumor classification, and localization, suPAR was significantly associated with mortality, HR 1.74 (1.33-2.26; p<0.0001). In addition, the suPAR level was associated with tumor stage and localization; and in colon cancer patients the suPAR level was significantly higher compared to rectal cancer patients5. The same cohort was also followed in another study, in which the suPAR plasma level was found to be an independent prognostic marker6.
To identify risk patients among elective colon cancer patients the suPAR level was studied. In patients receiving blood transfusion during surgery, the suPAR level was higher, and a significant association between the suPAR level and postoperative infections was shown. Occurrence of pneumonia was significantly associated with the suPAR level, but any significant association with other infectious complications could not be found7.
In patients with gastric cancer, the suPAR level was significantly higher compared to healthy controls (2.3 ng/mL ± 0.77), and the suPAR level was significantly higher in cancer patients with metastatic disease (7.0 ng/mL ± 6.1) than in patients with no metastases (4.8 ng/mL ± 4.4). In the group of patients with a suPAR value above 5.2 ng/mL, the mortality was significantly increased8.
In patients with rectal cancer9 and colon cancer10, a similar prognostic value is found, indicating an increased mortality risk.
suPAR in orthopedic surgery
The diagnostic value of suPAR in prosthetic knee/hip joint infection has been examined in a study. The study included 80 patients of which 45 experienced prosthetic joint infection defined by presence of clinical signs (swelling, redness, tenderness, and pus inside the joint) and a positive culture. In these patients, a significantly higher median suPAR level (6.8 ng/mL) was found compared to patients without infection, who had revision surgery done. Furthermore, suPAR was positively correlated with CRP, and the study showed that suPAR was more precise in diagnosing prosthetic knee/hip joint infection than CRP11.
2. Biccard BM, Devereaux PJ, Rodseth RN. Cardiac biomarkers in the prediction of risk in the non-cardiac surgery setting. Anaesthesia 2014; 69: 484-493.
3. Østervig RM, Køber L, Forberg JL, Rasmussen LS, Eugen-Olsen J, Iversen K. suPAR—a future prognostic biomarker in emergency medicine. Scand J Trauma Resusc Emerg Med 2015;23(Suppl 1):A31.
4. Kjellman A, Akre O, Gustafsson O et al. Soluble urokinase plasminogen acitvator receptor as a prognostic marker in men participating in prostate cancer screening. J. intern Med. 2011 Mar;269(3):299-305.
5. Lomholt AF, Christensen IJ, Høyer-Hansen G et al. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients. Acta Oncology 2010; 49:805-811
6. Stephens RW1, Nielsen HJ, Christensen IJ, Thorlacius-Ussing O, Sørensen S, Danø K, Brünner N. Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis.J Natl Cancer Inst. 1999 May 19;91(10):869-74.
7. Svendsen MN, Ytting H, Brünner N et al. Preoperative concentrations of suPAR and MBL proteins are associated with the development of pneumonia after elective surgery for colorectal cancer. Surg Infect (Larchmt) 2006 okt;7(5): 463-471.
8. Fidan E, Mentese A, Ozedemir F. Diagnostic and prognostic significance of CA IX and suPAR in gastric cancer. Med oncol 2013 jun;30(2):540
9. Fernebro E, Madsen RR, Fernö M et al. Prognostic importance of the soluble plasminogen activator receptor, suPAR, in plasma from rectal cancer pateints. Eur j cancer 2000; 486-491.
10. Stephens RW, Nielsen HJ, Christensen IJ. Plasma urokinase recptor levels in patients with colorectal cancer: relationship to prognosis. J natl Cancer Inst 1999, 91, 869-874.
11. Galliera E, Drago L, Marazzi MG. Soluble urokinase-type plasminogen activator receptor (suPAR) as new biomarker of the prosthetic joint infection: correlation with inflammatory cytokines. Clin Chim Acta 2015 Feb 20;414:23-8.See comment in PubMed Commons below
12. Alstrup M et al. Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Added Predictor to Existing Preoperative Risk Assessments. World J Surg. 2019 43(3):780-790
13. Meyer J et a..suPAR is associated with risk of future acute surgery and post-operative mortality in acutely admitted medical patients. Scand J Trauma Resusc Emerg Med. 2018 Feb 1;26(1):11.