Key Publications about suPAR
suPAR Publications and links
Please always find our latest list of suPAR Publications and links to PubMed here:
The same PubMed list grouped by Organ and Disease here:
Find the full list of suPAR abstracts in PubMed here:
On the basis of more than 600 published articles on suPAR in PubMed, a suPAR Monograph has been written.
Here you can find a short summary of the research done on suPAR within 12 groups of disease areas and see how the suPAR level is affected within each kind of disease.
The summary of each disease area is also found under Clinical Use here.
Key suPAR publications
“Soluble Urokinase Plasminogen Activator Receptor (suPAR) is predictive of Non-AIDS Events during Antiretroviral Therapy-mediated Viral Suppression” published in Clinical Infectious Diseases.
HIV infection remains associated with higher morbidity/mortality, partly driven by increased inflammation. The study by Martin Hoenigl et al. examines associations between levels of plasma biomarkers of chronic inflammation, microbial translocation, and monocyte activation, measured prior to and during suppressive ART, with occurrence of non-AIDS events.
Higher levels of suPAR were associated with increased risk of non-AIDS events. Higher levels of BDG and LBP at year one and pre-event were associated with increased risk of non-AIDS events. No associations were observed for other biomarkers.
The study concludes that elevated levels of suPAR were strongly, consistently and independently predictive of non-AIDS events at every measured time point. Interventions that target the suPAR pathway should be observed to explore its role in the pathogenesis of non-AIDS-related outcomes in HIV-infection.
“Soluble urokinase plasminogen activator receptor associates with higher risk, advanced disease severity as well as inflammation, and might serve as a prognostic biomarker of severe acute pancreatitis” published in Journal of Clinical Laboratory Analysis.
This study aimed to explore the potential of suPAR as a biomarker for severe acute pancreatitis (SAP) risk prediction and disease management in SAP patients. It was conducted at the First Affiliated Hospital of Harbin Medical University in China with 225 acute pancreatitis (AP) patients. The suPAR level was increased in SAP patients compared with MSAP patients, MAP patients and HCs.
The authors conclude that suPAR is of good predictive value for SAP risk and may serve as a potential biomarker for disease severity, inflammation, and in hospital mortality in SAP patients.
“The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma – a retrospective cohort study” published in Respiratory Research.
The biomarker suPAR has been associated with asthma control and with prognosis in acutely admitted medical patients. This study by KEJ Håkansson and coworkers investigates if suPAR and blood eosinophil counts at the time of admission for asthma are associated with readmission and mortality.
The study included 1341 patients who were acutely admitted to Hvidovre Hospital in Denmark with an asthma diagnosis. In comparison to event-free patients, patients that were readmitted or that died had significantly higher suPAR concentrations (p<0.0001) and lower eosinophil counts (p = 0.0031) at admission.
The authors conclude that elevated suPAR levels, together with the eosinophil count, were associated with 365-day readmission and mortality in patients acutely admitted with asthma.
“Association of Adverse Experiences and Exposure to Violence in Childhood and Adolescence With Inflammatory Burden in Young People” published in Jamapedriatrics.
Line JH Rasmussen and coworkers investigated whether exposure to stress and violence in childhood leads to elevated suPAR levels in adulthood.
1391 participants from a 1994 to 1995 birth cohort of twins were followed up until they reached 18 years of age. Individuals exposed to multiple types of violence in both childhood and adolescence had higher suPAR levels compared with children who did not experience stress or violence. They were significantly more likely to have elevated suPAR levels even if they did not have elevated CRP or IL-6 levels.
The results suggest that adult inflammation is highly associated with childhood exposure to stress. Adding suPAR to traditional biomarkers may improve measurement of stress-related inflammatory burden.
“High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma” published in Carcinogenesis.
Many pancreatic adenocarcinoma (PDAC) patients are still facing an unfavorable prognosis after complete tumor resection, meaning that better preoperative stratification algorithms are needed. The study by Sven H Loosen and coworkers explored the role of suPAR for patients undergoing resection.
PDAC patients had a significantly elevated suPAR level compared to the healthy control group and patients with PDAC precursor lesions. Patients with a high preoperative suPAR level also showed a significantly reduced overall survival after resection. The prognostic role of suPAR was further reinforced by Cox-regression analyses and high suPAR levels also identified patients particularly susceptible to acute kidney injury and surgical complications after surgery.
The study concludes that suPAR might be a useful addition to existing preoperative stratification algorithms for identifying patients that benefit from extended tumor resection.
“Soluble Urokinase Plasminogen Activator Receptor Predicts Cardiovascular Events, Kidney Function Decline, and Mortality in Patients With Type 1 Diabetes” published in Diabetes Care.
Despite being an important inflammatory biomarker implicated in endothelial and podocyte dysfunction, suPAR’s predictive qualities for complications in type 1 diabetes have yet to be determined. This study by Viktor Rotbain Curovic et al., including 667 participants, investigated the value of suPAR for the prognostic value for the development of cardiovascular events, decline in renal function, and mortality in patients with type 1 diabetes.
A higher level of suPAR showed to be a significant and independent risk factor for cardiovascular events, decline in eGFR ≥30%, and mortality. suPAR also significantly contributes to discrimination for the end points.
“Early Discharge from the Emergency Department Based on Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels: A TRIAGE III Substudy” published in Disease Markers.
The authors of this study investigated whether the prognostic biomarker suPAR can help in the early identification of patients at low risk of serious illness. 16.801 acutely admitted patients at two university hospitals in the Capital Region of Denmark were compared related to whether they had a valid supAR measurement at admission or not.
The proportion of patients who were discharged within 24 hours of admittance was significantly higher in the suPAR group compared to the control group (50.2% vs. 48.6%), while mean length of hospital stay in the suPAR group was shorter compared to the control group (4.3 days vs. 4.6 days). In contrast, the readmission rate within 30 days was higher in the suPAR group (10.6% vs. 8.8%). Among patients discharged within 24 hours, there was no significant difference in the readmission rate or mortality within 30 days.
The study demonstrates that the availability of suPAR was associated with a higher proportion of discharge within 24 hours and reduced length of stay, but more readmissions. In patients discharged within 24 hours, there was no difference in readmission or mortality.
“Availability of suPAR in emergency departments may improve risk stratification: a secondary analysis of the TRIAGE III trial” published in Scandinavian journal of trauma, resuscitation and emergency medicine.
The blood level of suPAR might be usable for the identification of ED patients at high-and low risk. This study by Martin Schultz and coworkers investigates the value of adding suPAR to triage and how this could impact risk stratification regarding mortality.
suPAR was significantly better in predicting mortality than triage. Combining suPAR and triage yielded an AUC of 0.87. The Youden’s index cut-off value of suPAR was 5.9 ng/ml and reclassified triage using this value resulted in a more accurate risk stratification regarding hospital admission and mortality.
The study concluded that adding suPAR to triage potentially improves short-term mortality prediction. Measurement of suPAR in relation to the triage process may allow a more accurate identification of ED patients at risk.
“Soluble urokinase plasminogen activator receptor is linearly associated with dietary quality and predicts mortality” published in British Journal of Nutrition.
suPAR is a stable marker of chronic inflammation, which is associated with disease risk and mortality. Higher levels of suPAR are found in individuals with an unhealthy lifestyle.
This study with 5347 participants by Peter BS Törnkvist and coworkers investigates the relation between suPAR and dietary quality measured with the dietary quality score (DQS). It also examines the association of both suPAR and the DQS with CVD risk and mortality in the general Danish population.
Multiple linear regression analyses showed a linear reverse association between the DQS and suPAR. Cox regression analyses showed an 18% increase in the risk of death from any cause with each 1 ng/ml increase in suPAR. There was no significant association between the DQS and the mortality.
The study confirms that low dietary quality may constitute a health risk through its influence on chronic inflammation. Further studies should investigate whether suPAR is modifiable through dietary changes.
“Healthy lifestyles reduce suPAR and mortality in a Danish general population study” published in Immunity and Ageing.
This study by Thomas H Haupt and coworkers investigated whether change in lifestyle habits impact the suPAR level, and whether the resultant levels are associated with mortality.
Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a higher suPAR. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR died compared to 3.8% of individuals with a high suPAR.
In conclusion, suPAR levels were considerably impacted by lifestyle. The combination of unhealthy habits was associated with 44% higher 5-year suPAR values and the 5-year suPAR was a strong predictor of mortality.
“Combining National Early Warning Score With suPAR Improves Risk Prediction in Acute Medical Patients:
A Registry-Based Cohort Study” published in Critical Care Medicine.
In this large study including more that 17.000 patients, Line JH Rasmussen and coworkers aimed to evaluate whether suPAR adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score, NEWS) in acute medical patients.
High suPAR was associated with in-hospital-, 30-day-, and 90-day mortality within all NEWS Score groups, in particular in patients with a low NEWS. Combining suPAR with NEWS, age, and sex in prediction of 30-day mortality, gave an AUC of 0.90 with a negative predictive value of 99.0%.
In patients with normal vital signs and high suPAR, risk may not be clinically recognized and fewer actions taken.
The authors conclude that using suPAR in combination with NEWS could potentially lead to clinical interventions among patients otherwise not considered urgent or at risk, thereby ultimately saving lives.
Finally, the high NPV found in this study may aid in hospital discharge decisions, and as anunspecific biomarker, the NPV may be of most clinical relevance in clinical decision-making.
May 21, 2018
“suPAR predicts mortality in exacerbated COPD” published in Respiratory Research.
The study by Nina Godtfredsen and coworkers hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure.
The study included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis. Primary outcomes were 30- and 90-days all-cause mortality.
suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P < 0.0001) and increasing suPAR levels independently predicted 30-day mortality in patients with a hazard ratio of 2.0 (95% CI 1.7-2.4).
The authors conclude that in acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality.
May 9, 2018
“Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood” published in Journal of Child Psychology and Psychiatry.
Line JH Rasmussen and co-workers from Duke University, USA, investigated the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood.
They used 837 participants in the Dunedin 1972-1973 birth cohort and found that children who experienced more adverse childhood experiences, had lower IQ, or had poorer self-control showed elevated adult suPAR.
The authors conclude that suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden.
May 2, 2018
“Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: suPAR, Coronary Artery Calcium, and High-Sensitivity C-Reactive Protein” published in JAHA.
Salim Hayek and co-workers measured suPAR in 500 African Americans with type 2 diabetes and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium, and high-sensitivity CRP.
After a median 6.8-year follow-up, a total of 68 deaths (13.6%) were recorded. In a model incorporating suPAR, CAC, and hs-CRP, only suPAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63-4.34).
Addition of suPAR to a baseline clinical model significantly improved the C-statistic for all-cause death (Δ0.05, 95% confidence interval 0.01-0.10), whereas addition of CAC or hs-CRP did not.
The authors conclude that suPAR was strongly associated with mortality and improved risk beyond traditional risk factors.
March 16, 2018
“Effect of simvastatin and ezetimibe on suPAR levels and outcomes”
published in Atherosclerosis.
suPAR is an inflammatory marker associated with cardiovascular disease. Statins lower both LDL-cholesterol and C-reactive protein (CRP) resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. The study included 1838 patients with mild-moderate, asymptomatic aortic stenosis, to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).
The study concluded that Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. The change in suPAR was associated with all-cause mortality, MCE, and AVE.
Find the publication by Hodges GW et al here: https://www.sciencedirect.com/science/article/pii/S0021915018301552
February 1, 2018
“suPAR is associated with risk of future acute surgery and post-operative mortality in acutely admitted medical patients” published in Scand J Trauma Resusc Emerg Med.
suPAR is known to be a strong predictor of readmission and mortality in the acute care setting. In this study, it was investigated if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality. The study included 17,312 acute medical patients. The risk of acute surgery during follow-up 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).
The study concluded 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 mortality.
Find the publication by Meyer J et al here: https://sjtrem.biomedcentral.com/articles/10.1186/s13049-018-0478-1
October 17, 2017
“Soluble Urokinase Plasminogen Activator Receptor Is a Predictor of Incident Non-AIDS Comorbidity and All-Cause Mortality in Human Immunodeficiency Virus Type 1 Infection” published in J Infect Dis.
The study investigated the potential association between suPAR and incident comorbidity and all-cause mortality in a well-treated HIV-infected population.
The study showed that a high suPAR level at baseline was associated with increased risk for cardiovascular disease, chronic kidney disease, chronic lung disease, liver disease, and cancer, and all-cause mortality during follow-up.
Find the publication by Kirkegaard-Klitbo DM et al here: https://academic.oup.com/jid/article/216/7/819/3916663
August 23, 2017
“A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease” published in Nature Medicine.
suPAR independently predicts chronic kidney disease incidence and progression.
In this paper, a causal relationship for developing kidney disease between suPAR, APOL1 and αvβ3 integrin is found to cause proteinuria in a suPAR-dependent manner.
Find the publication by Hayek SS et al here: https://www.nature.com/articles/nm.4362
September 2, 2016
“suPAR in acute care: A strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study” was published online in EMJ, Emergency Medical Journal in September 2016.
The study included 4343 consecutively admitted patients from the AMU at a large Danish university hospital (Hvidovre).
The conclusion is again, that in an unselected population of acute medical patients;
“A high suPAR level upon admission to the AMU is a marker of severe disease and increased risk of readmission and mortality after adjusting for all other risk factors …. and suPAR adds information to established prognostic indicators”.
Patients with low suPAR levels have low risk of readmission and mortality, while patients with high suPAR levels have a high risk of adverse events.
Please find the publication hereLine J.H.Rasmussen et al from EMJ
November 10, 2015
A study in the New England Journal of Medicine published on November 5 shows that suPAR reliably can predict the development of Chronic Kidney Disease up to five years before symptoms of this disease emerge – a disease that affects an estimated 600 million people.
Currently, physicians rely on two markers to monitor existing kidney disease, but they are not sensitive enough to predict a persons risk of developing the disease or to catch it in its early stages.
The New England Journal of Medicine study found that a high suPAR level was an excellent predictor of future kidney disease.
“We can now stratify people according to their risk of developing kidney disease using suPAR levels” said Dr. Salim Hayek, first author of the study.
The study is even a significant breakthrough in preventive medicine. Also diabetes patients, of which about one-third develop Diabetic Kidney Disease, can now be helped.
“This will help risk-stratify patients with diabetes on their risk of future kidney disease” explains Jochen Reiser, senior author of the NEJM study.
Results are based upon research using the suPARnostic® products from ViroGates.
The New England Journal of Medicine article and abstract
An editorial explaining and commenting on the data
ScienceDaily comment on the data set