Soluble Urokinase Plasminogen Activator Receptor Research Articles

SuPAR is associated with death and adverse cardiovascular outcomes in patients with suspected coronary artery disease

Background The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with presence and severity of coronary artery disease (CAD) and incident death and myocardial infarction (MI). We sought to validate this finding in a further cohort of patients with suspected CAD. Methods Plasma suPAR was available in 1635 patients (73% with CAD) undergoing coronary angiography at a single regional Danish hospital between 2003 and 2005. Patients were followed for adverse cardiovascular outcomes of death, cardiac death and MI over a median follow-up of 4.2 years. Results In multivariate Cox models, adjusted for established cardiovascular risk factors, the biomarkers C-reactive protein, troponin-T and N-terminal-pro brain natriuretic peptide and the number of stenotic vessels, suPAR was independently associated with the combined endpoint of death/MI, hazard ratio (HR) 1.88; cardiovascular death, HR 2.01; and non-fatal MI, HR 1.53; (all p ≤ .037) per doubling of suPAR concentration. A plasma cutoff for suPAR ≥ 3.5 ng/mL was also significantly associated with death/MI, HR 1.51; p = .005. The C-statistic for the multivariate model predicting death/MI improved from 0.712 to 0.730 (p for difference .008) after inclusion of suPAR. However, suPAR was not associated with presence or extent of CAD (p > .05). Conclusion These results validate previous findings that demonstrate suPAR to be an independent predictor of death/MI in patients with suspected or known CAD, however suPAR was not associated with presence or extent of CAD in our cohort. Probably because suPAR reflects end organ damage rather than the degree of atherosclerosis. BRIEF SUMMARY We demonstrate that the inflammatory biomarker soluble urokinase plasminogen activator receptor is an independent predictor of death/myocardial infarction in patients with suspected or known coronary artery disease, but is not associated with the presence or severity of coronary artery disease.

Prognostic Role of Soluble Urokinase Plasminogen Activator Receptor at the Emergency Department: A Position Paper by the Hellenic Sepsis Study Group

In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of this statement is that sUPAR is a non-specific marker associated with a high negative predictive value for unfavourable outcomes; levels < 4 ng/ml indicate that it is safe to discharge the patient, whereas levels > 6 ng/ml are an alarming sign of risk for unfavourable outcomes. However, the suPAR levels should always be interpreted in light of the patient's history.

Effects of a highly controlled carbohydrate-reduced high-protein diet on markers of oxidatively generated nucleic acid modifications and inflammation in weight stable participants with type 2 diabetes; a randomized controlled trial

Carbohydrate-restricted diets are increasingly recognized as options for dietary management of type 2 diabetes mellitus (T2DM). We investigated the effects of a carbohydrate-reduced high-protein (CRHP) and a conventional diabetes (CD) diet on oxidative stress and inflammation in weight stable individuals with T2DM. We hypothesized that the CRHP diet would improve markers of oxidatively generated RNA and DNA modifications as well as inflammatory parameters. Thirty participants with T2DM were randomized to 6 weeks of CRHP or CD dietary treatment (30/50 energy percentage (E%) carbohydrate, 30/17E% protein, 40/33E% fat), followed by a cross-over to the opposite diet for a subsequent 6-week period. All meals were provided during the study and body weight was controlled. Diurnal urine samples were collected after 4 weeks on each diet and oxidatively generated RNA and DNA modifications were measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), respectively. Fasting concentrations of soluble urokinase plasminogen activator receptor, high-sensitivity C-reactive protein, tumor necrosis factor alpha and interleukin-6 were measured before and after 6 weeks of interventions. Compared with the CD diet, the CRHP diet increased 24-hour urinary excretion of 8-oxoGuo by 9.3% (38.6 ± 12.6 vs. 35.3 ± 11.0 nmol/24 h, p = .03), whereas 8-oxodG did not differ between diets (24.0 ± 9.5 vs. 24.8 ± 11.1 nmol/24 h, p = .17). Changes in plasma inflammatory parameters did not differ between CRHP and CD diets, all p ≥ .2. The clinical implications of increased RNA oxidation following a CRHP diet as well as long-term effects of carbohydrate-restriction on markers of oxidatively generated nucleic acid modifications should be a field of future study.

Seroprevalence of Helicobacter pylori/CagA Antibodies in Guatemalan Gastric Cancer Patients: Association of Seropositivity with Increased Plasma Levels of Pepsinogens but not Soluble Urokinase Plasminogen Activator Receptor.

Infection by Helicobacter pylori is a major risk factor for gastric cancer (GC), the second leading cause of cancer-related death worldwide. Although biomarkers such as pepsinogens (PGs) and soluble urokinase plasminogen activator receptor (suPAR) may have diagnostic and/or prognostic value in patients with GC, their levels may be affected by H. pylori infection. The aim of this study was to investigate the association of the presence of antibodies to H. pylori and cytotoxin-associated gene A (CagA) with plasma levels of PGs and suPAR in a cohort of Guatemalan GC patients and controls. To this end, levels of suPAR, Pepsinogens I and II (PGI and PGII), and antibodies to H. pylori and CagA toxin were determined by ELISA in plasma samples from 67 GC patients and 136 matched healthy controls. Seropositivity for CagA was significantly higher in patients with GC than in controls. Pepsinogens II and suPAR levels were higher and PGI/PGII ratios were lower in GC patients than in controls. There was a significant association of H. pylori seropositivity status with increased levels of PGII and lower PGI/PGII ratios, particularly in the control (non-GC) population. The levels of suPAR were not significantly affected by H. pylori or CagA seropositivity status. These results suggest that the seropositivity status for H. pylori and CagA need to be taken into account during the GC diagnostic process.

Beneficial Effects of Cannabis on Blood-Brain Barrier Function in Human Immunodeficiency Virus.

Human immunodeficiency virus (HIV) infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. We studied persons with HIV (PWH) and HIV-negative (HIV-) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay. Participants were 45 PWH and 30 HIV- individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r = 0.47, P < .001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean ± SD, 0.361 ± 1.20 vs -0.501 ± 1.11; P = .0214). HIV serostatus interacted with cannabis use frequency, such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV- individuals. Worse BBB index values were associated with higher NFL in CSF (r = 0.380, P = .0169). Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.

The Plasma Soluble Urokinase Plasminogen Activator Receptor Is Related to Disease Activity of Patients with ANCA-Associated Vasculitis

Objective The soluble urokinase plasminogen activator receptor (suPAR) is associated with kidney diseases and is used as a prognostic factor of renal function progression. The aim of this study was to explore whether circulating suPAR was associated with antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) disease activity. Methods We evaluated 90 AAV patients with follow-up data and 35 normal controls; their plasma suPAR and C-reactive protein (CRP) levels were measured by ELISA. Associations between these levels, clinical parameters, and prognosis were analyzed. Results Plasma suPAR levels in AAV patients were significantly higher than in healthy controls (5,920.08 ± 3,447.17 vs. 1,441.97 ± 835.04 pg/mL, P < 0.001). Furthermore, suPAR was significantly elevated in AAV patients in active stage compared to those in partial remissions (6,492.19 ± 3,689.48 vs. 5,031.86 ± 2,489.01 pg/mL, P = 0.039). Correlation analyses demonstrated that suPAR levels positively correlated with initial serum creatinine, BVAS, CRP, and procalcitonin concentration, and negatively correlated with eGFR and C3 circulating levels. In a Kaplan-Meier survival analysis, patients with plasma suPAR levels >5683.3 pg/mL showed poorer survival than patients with lower levels (log-rank, P = 0.001). Besides, multivariate analyses confirmed that plasma suPAR levels were an independent adverse prognostic factor for a composite outcome of end-stage renal disease (ESRD) or death, after adjusting for age and gender (HR 1.05, 95% CI = 1.01 − 1.11, P = 0.043). Receiver operating characteristic curves showed a suPAR cutoff value >6662.2 pg/mL for composite outcome with 68% sensitivity and 88% specificity, with an AUC = 0.82, (95% CI = 0.68 − 0.96, P < 0.001). Conclusion Circulating suPAR levels might be a marker of activity correlated with disease activity in AAV patients, and, to some extent, could be a factor of poor prognosis.

High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD.

IntroductionThe biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD.MethodsThis retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein.ResultssuPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40–1.85; p<0.0001) and 3.40 (95% CI 2.64–4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/μL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39–0.62; p<0.0001) compared with patients with <150 cells/μL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/μL) group.ConclusionIn this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.

Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study.

Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted for clinical practice. Methods: Plasma concentrations of five cardiovascular biomarkers (soluble suppression of tumorigenicity (sST2), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor-binding protein 2 (IGF-BP2), and soluble urokinase plasminogen activator receptor) were analyzed by means of enzyme-linked immunosorbent assay (ELISA) in 219 patients with CKD enrolled in the German Chronic Kidney Disease (GCKD) study. Results: Except for sST2, all of the investigated biomarkers were significantly elevated in patients with CKD (2.0- to 4.4-fold increase in advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² body surface area (BSA)) and showed a significant inverse correlation with eGFR. Moreover, all but H-FABP and sST2 were additionally elevated in patients with micro- and macro-albuminuria. Conclusions: Based on our findings, sST2 appears to be the biomarker whose diagnostic performance is least affected by decreased renal function, thus suggesting potential viability in the management of patients with CVD and concomitant CKD. The predictive potential of sST2 remains to be proven in endpoint studies.

Assessment of saliva and gingival crevicular fluid soluble urokinase plasminogen activator receptor (suPAR), galectin‐1, and TNF‐α levels in periodontal health and disease

The aim of the study is to evaluate saliva and gingival crevicular fluid (GCF) levels of suPAR and galectin-1 in different periodontal health status and relationship between these molecules and TNF-α to understand the roles of these molecules in periodontal inflammation process. Soluble urokinase plasminogen activator receptor (suPAR) has been described as a biological marker of inflammation and immunological activation. Galectin-1, a member of the galectin family, is an anti-inflammatory cytokine. However, to date, levels of these two molecules in periodontal health and disease have not been well documented. A total of 60 individuals, 20 with chronic periodontitis (group P), 20 with gingivitis (group G), and 20 with healthy periodontium (group H) were recruited for this study. Full-mouth clinical periodontal measurements were recorded in periodontal charts. GCF and whole saliva samples were collected to determine the levels of suPAR, galectin-1, and TNF-α in study groups using enzymelinked immunosorbent assay (ELISA) method. The GCF total amount of suPAR, galectin-1, and TNF-α in GCF was similar in group P and G (P>.05). The GCF total amounts of these molecules in GCF were higher in the group G and P compared to the group H (P<.05), whereas the GCF concentrations of suPAR and galectin-1 were lower in the group G and P compared to the group H (P<.05).The saliva concentration of suPAR was significantly higher in group P compared to the group G and H (P<.05). It was also higher in the group G compared to the group H but there is no significant difference between the groups (P>.05). Salivary galectin-1 levels were similar in the study groups (P>.05). Increased levels of GCF suPAR, galectin-1, and saliva suPAR in periodontal disease suggest that these molecules may play a role in the periodontal inflammation. suPAR and galectin-1 may be considered as potential biomarkers in periodontal disease.

Soluble urokinase plasminogen activator receptor (suPAR) as a biomarker of early pregnancy location and viability compared with hCG, progesterone and estradiol

A circulating biomarker of early pregnancy outcome independent of ultrasonography and gestational age is a coveted goal. This study evaluated soluble urokinase plasminogen activator receptor (suPAR), a well-described marker of inflammation and immunological activation, for this purpose, and compared it with established early pregnancy biomarkers of the luteoplacental phase: progesterone, estradiol and hCG. We merged data from two prospective first trimester cohorts to conduct a case-control study comparing these analytes in women who had either a live birth, a miscarriage or an ectopic pregnancy. The ability to predict pregnancy location and viability was assessed by areas under the receiver operating characteristic curves (AUC). Comparing women irrespective of gestational age with a live birth, miscarriage or ectopic pregnancy showed significantly lower suPAR values in the latter group (2.4 vs. 2.4 vs. 2.0 μg/L, p = 0.032, respectively), as were all other analytes. Before 6 weeks’ gestation, suPAR was significantly inferior to progesterone, estradiol and hCG in pregnancy location and viability prediction (in 124 pregnancies, suPAR AUClocation = 0.69 [CI: 0.54–0.83] and AUCviability = 0.58 [CI: 0.48–0.69], while progesterone AUClocation = 0.95 [CI: 0.87–1.00] and AUCviability = 0.84 [CI: 0.75–0.92]). After 6 weeks’ gestation, suPAR prediction improved but was inferior to hCG, progesterone and estradiol (in 188 pregnanices, suPAR AUClocation = 0.71 [CI: 0.63–0.78] and AUCviability = 0.70 [CI: 0.63–0.78] compared with hCG AUClocation = 0.96 [CI: 0.93–0.99] and AUCviability = 0.96 [CI: 0.93–0.98]). Collectively, suPAR is less useful as a predictor of early pregnancy outcome than hCG, progesterone and estradol.

Circulating levels of soluble urokinase plasminogen activator receptor (suPAR) to predict outcome after resection of biliary tract cancer.

572 Background: Surgical resection is the only curatively intended 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 preoperative stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has recently been associated with cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing resection of BTC. Methods: Tumor expression of uPAR, the membrane bound source of suPAR, was analyzed by IHC in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 BTC patients and 76 healthy controls. Results: A high tumoral uPAR expression was associated with an adverse outcome after BTC resection. In line, circulating levels of suPAR were significantly elevated in BTC patients compared to healthy controls and patients with primary sclerosing cholangitis (PSC). Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72ng/ml for BTC patients. 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 clinicopathological parameters such as the tumor stage, markers of systemic inflammation or organ dysfunction and established tumor markers revealed suPAR as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative for acute kidney injury after tumor resection. Conclusions: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might be useful to preoperatively identify the ideal candidates for tumor resection.

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer.

Background & AimsSurgical 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.MethodsTumor 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.ResultsHigh 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.ConclusionCirculating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery.Lay summarySurgical 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.

Soluble Urokinase Receptor and Acute Kidney Injury

BackgroundAcute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target.MethodsWe measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR.ResultsThe suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells.ConclusionsHigh suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.)

Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children

Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. Prospective longitudinal cohort study. 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P< 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P= 0.008). Plasma suPAR levels showed little change over 6 months. Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.

Effect of remission induction therapy on the level of soluble urokinase plasminogen activator receptor in acute myeloid leukemia

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) in acute myeloid leukemia (AML) is associated with resistance to chemotherapy. The aim is to assess the effect of remission induction on plasma level of suPAR in AML patients and to correlate between plasma levels of suPAR with certain hematological parameters, AML subtypes, and extramedullary involvement.MATERIALS AND METHODS: The study was conducted on 30 newly diagnosed adult AML patients and 20 controls. The peripheral blood and bone marrow smears were examined at diagnosis and after remission induction therapy to assess complete remission (CR). The plasma level of suPAR was measured by enzyme immunoassay which was done at diagnosis and after remission induction therapy.RESULTS: Plasma suPAR level was higher in AML patients at presentation than the control group (P < 0.001). The plasma level of suPAR revealed a significant reduction in the 37% of patients who achieved CR or partial response (P = 0.004), whereas the differences were insignificant and remained high in patients who did not show response (P = 0.573). Before and after treatment, there were insignificant differences in suPAR level in patients with or without extramedullary involvement and in various AML subgroups (P > 0.05). The suPAR levels were high before starting treatment in both the alive and those who deceased (P = 0.984). After 5 months of follow-up, it showed a significant reduction among the alive group (P = 0.001). There were insignificant correlations between the level of uPAR and hematological parameters at presentation.CONCLUSIONS: The reduction of plasma suPAR level is associated with a better response, and a high level is associated with a high risk of death. Before and after induction therapy, there is no association between plasma level of suPAR in monocytic group, nonmonocytic group, and in patients with or without extramedullary involvement. Plasma suPAR level is uncorrelated with hematological parameters at presentation.

Further Evidence That the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes.

The role of the soluble urokinase plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis (FSGS) as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Previously published studies in mice and isolated podocytes produced conflicting results on the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria. These discordant results were in part due to diverse experimental designs and different strains of mice. The aim of our study was to determine the reasons for the inconsistencies of the previous studies results with suPAR by using uniform methods and studies in different strains of mice. We utilized a primary culture of human podocytes and 2 mouse models, the wild type (WT) and the urokinase plasminogen activator receptor (uPAR) KO (uPAR), in an attempt to resolve the reported conflicting results. In both WT and uPAR mouse models, injection of recombinant uPAR, even at a high dose (100 μg), did not induce proteinuria, effacement of podocytes, or disruption of the cytoskeleton. Injection of suPAR resulted in its deposition exclusively in the glomerular endothelial cells and not in the podocytes of WT mice and was not detected at the uPAR KO mice. Kidneys from patients with recurrent FSGS had negative immunostaining for uPAR. We also evaluated the effect of recombinant uPAR on primary culture of human podocytes. uPAR did not result in podocytes damage. suPAR by itself is not the cause for direct podocyte injury, in vitro or in vivo. These findings suggest a more complex and still poorly understood role of suPAR in FSGS.

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.

BackgroundThis study aimed to explore the potential of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker for severe acute pancreatitis (SAP) risk prediction and disease management in SAP patients.MethodsTotally 225 acute pancreatitis (AP) patients (including 75 SAP, 75 moderate‐severe acute pancreatitis [MSAP], and 75 mild acute pancreatitis [MAP] patients) were recruited based on the Atlanta classification, and their serum samples were obtained within 24 hours after admission. Meanwhile, 75 health controls (HCs) were recruited with their serum samples collected at the enrollment. The serum suPAR was then detected using enzyme‐linked immunosorbent assay.ResultsThe suPAR level was increased in SAP patients compared with MSAP patients (P = .023), MAP patients (P < .001), and HCs (P < .001). Receiver operating characteristic (ROC) curve presented that suPAR could not only differentiate SAP patients from HCs (AUC: 0.920, 95%CI: 0.875‐0.965) but also differentiate SAP patients from MSAP (AUC: 0.684, 95%CI: 0.600‐0.769) and MAP patients (AUC: 0.855, 95%CI: 0.797‐0.912). In SAP patients, suPAR was positively correlated with Ranson score (P < .001), acute physiology and chronic healthcare evaluation II score (P = .001), sequential organ failure assessment score (P < .001), and C‐reaction protein (P = .002). Further ROC curve exhibited that suPAR (AUC: 0.806, 95%CI: 0.663‐0.949) was of good value in predicting increased inhospital mortality of SAP patients.ConclusionSoluble urokinase plasminogen activator receptor is of good predictive value for SAP risk and may serve as a potential biomarker for disease severity, inflammation, and inhospital mortality in SAP patients.

The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma \u2013 a retrospective cohort study

IntroductionPrognostic biomarkers in asthma are needed. The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with asthma control and with prognosis in acutely admitted medical patients. We investigated if suPAR and blood eosinophil counts at the time of admission for asthma are associated with readmission and mortality.MethodsOur cohort comprised 1341 patients (median age 45.3, IQR 30.1–63.1) acutely admitted with a diagnosis of asthma to Hvidovre Hospital, Denmark (November 2013 to March 2017). Patients had suPAR and blood eosinophils measured at admission. Outcomes were 365-day readmission and all-cause mortality. Logistic regression analysis adjusted for age, sex, C-reactive protein, and Charlson comorbidity score was used to assess the association of the two biomarkers with readmission and all-cause mortality.ResultsCompared to event-free patients, patients who were either readmitted (n = 452, 42.3%) or died (n = 57, 5.3%) had significantly higher suPAR concentrations (p < 0.0001) and lower eosinophil counts (p = 0.0031) at admission. The highest odds of readmission or mortality were observed for patients in either the 4th suPAR quartile (p < 0.0001) or with eosinophil counts < 150 cells/μL at admission. Increasing levels of suPAR were associated with 365-day readmission (OR 1.3 [1.0–1.6]; p = 0.05) and mortality (OR 2.9 [1.7–5.1]; p = 0.0002). Eosinophil count > 300 cells/μL was significantly associated with lower odds of readmission (OR 0.64 [0.5–0.9]; p = 0.005) and lower mortality (OR 0.7 [0.6–0.9]; p = 0.0007).ConclusionsIn patients acutely admitted with asthma, elevated suPAR concentrations together with blood eosinophil count < 150 cells/μL at the time of hospital admission were associated with both 365-day all-cause readmission and mortality.

The role of soluble urokinase plasminogen activator receptor (suPAR) in the diagnostics of diabetic foot infection

Background: To investigate the role of soluble urokinase plasminogen activator receptor (suPAR) in the diagnosis of diabetic foot infection and to determine whether it is superior to other infection markers like leukocyte, neutrophil, erythrocyte sedimentation rate, c-reactive protein and procalcitonin.Methods: The present prospective study consisted of four groups: Group 1, healthy volunteers (n = 38); Group 2, patients without diabetic foot ulcers (n = 40); Group 3, diabetic patients with uninfected foot ulcers (n = 33); and Group 4, patients who had diabetic foot infection (n = 48). In each group, the leukocyte, neutrophil, erythrocyte sedimentation rate, c-reactive protein and procalcitonin and suPAR levels were examined. The results were then statistically compared. In addition, the patients in Group 4 were further divided according to the presence of mild, moderate, and severe infection. Also osteomyelitis were evaluated in Group 4 and statistically compared.Results: All infection markers were significantly higher in group 4 patients than those in the other three groups (p < .05). Similarly, all infection markers in the severe diabetic foot infection group were statistically higher than mild diabetic foot infection group (p < .05); however, only suPAR and erythrocyte sedimentation rate were significantly high in cases with osteomyelitis (p < .05). In the receiver operating characteristic analysis, the optimal cut-off value for suPAR was determined to be 2.8 ng/ml, and the sensitivity and specificity above this value were 95.8% and 82.8%, respectively.Conclusions: The current study demonstrated that suPAR might be used as a supportive diagnostic method for the diagnosis of diabetic foot infections.

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort.

The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1-19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17-1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58-2.29), and suPAR (HR: 1.35, 95% CI: 1.17-1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol (p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.