Soluble Urokinase-type Plasminogen Activator Receptor Research Articles

Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Contrast-Induced Acute Kidney Injury in Percutaneous Coronary Intervention Patients

Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Contrast-Induced Acute Kidney Injury in Percutaneous Coronary Intervention Patients

Surface confinement–induced electrochemiluminescence enhancement of Au nanoclusters for ultrasensitive detection of a soluble urokinase-type plasminogen activator receptor

In this study, gold nanoclusters (Au NCs) anchored on the surface of 2D Zn-containing hydroxyl double salt (Zn-HDS) with surface confinement–induced electrochemiluminescence (SC-ECL) improvement were used as an intensive ECL emitter to construct a biosensor for ultrasensitive detection of soluble urokinase-type plasminogen activator receptor (suPAR) related to cardiovascular disease in chronic nephritis patients. Impressively, SC-ECL of Au NCs/Zn-HDS nanocomposites exhibited fast electrochemical excitation and efficient radiation transition, showing 4.9 times stronger ECL emission and 10.9 times higher ECL efficiency than those of pure Au NCs. This improvement was attributed to the matched energy level of Zn-HDS and Au NCs, enabling electron–hole pairs of Au NCs to be trapped by the energy levels of Zn-HDS. Moreover, a bipedal DNA walker was generated through target-induced DNA strand displacement and catalytic hairpin assembly (CHA), which was attached to a stable DNA cubic track through electrostatic attraction of positively charged SH-PEG-NH3+ to improve walking efficiency and further boost detection sensitivity. Consequently, the proposed sensing platform achieved trace detection of suPAR ranging from 0.700 pg/mL to 80.0 ng/mL with a low detection limit of 0.344 pg/mL and was successfully applied to detect suPAR in patient serum. This work synthesized a highly efficient metal nanocluster-based ECL emitter, showing great potential in constructing ultrasensitive biosensors for early disease diagnosis.

Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/μL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033). Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

MicroRNAs are associated with cardiac biomarkers, cardiac structure and function and incident outcomes in heart failure.

The association between microRNAs (miRNAs) and established cardiac biomarkers is largely unknown. We aimed to measure the association between plasma miRNAs and N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin I, soluble urokinase-type plasminogen activator receptor (suPAR), and galectin-3 with cardiac structure and function and clinical outcomes. We quantified 32 plasma miRNAs using the FirePlex miRNA assay and measured biomarkers in 139 individuals with symptomatic heart failure (HF). We used principal component (PC) analysis and linear regression to evaluate the association between miRNAs and biomarkers with ventricular size and function by echocardiography and Cox modelling for the incidence of a first composite event of HF hospitalization, heart transplant, left ventricular assist device implant, or death. The mean (standard deviation) age at baseline was 64.3 (12.4) years, 33 (24%) were female, and 122 (88%) were White. A total of 45 events occurred over a median follow-up of 368 (interquartile range 234, 494) days. Baseline NT-proBNP (β=-2.0; P=0.001) and miRNA PC2 (β=2.6; P=0.002) were associated with baseline left ventricular ejection fraction. NT-proBNP (β=20.6; P=0.0004), suPAR (β=-39.6; P=0.005), and PC4 (β=21.1; P=0.02) were associated with baseline left ventricular end-diastolic volumes. NT-proBNP [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.28-2.18, P=0.0002], galectin-3 (HR 2.02, 95% CI 1.05-3.91, P=0.036), PC3 (HR 1.75, 95% CI 1.23-2.49, P=0.002), and PC4 (HR 1.67, 95% CI 1.1-2.52, P=0.016) were independently associated with incident events. Biomarkers and miRNA PCs are associated with cardiac structure and function and incident cardiovascular outcomes. Combining information from miRNAs provides prognostic information beyond biomarkers in HF.

Soluble urokinase-type plasminogen activator receptor as biomarker of intra-amniotic inflammation in vaginally collected amniotic fluid

Soluble urokinase-type plasminogen activator receptor as biomarker of intra-amniotic inflammation in vaginally collected amniotic fluid

Clinical value of soluble urokinase-type plasminogen activator receptor in predicting sepsis-associated acute kidney injury

Background Sepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients. Methods We prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves. Results Of 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p < 0.05). The plasma suPAR had the highest area under the ROC curve of 0.700 (95% confidence interval (CI), 0.621–0.779) at 24-h post-sepsis diagnosis, at which the best discrimination ability for S-AKI was achieved with suPAR of ≥6.31 ng/mL (sensitivity 61.9% and specificity 71.6%). Logistic regression analysis showed that suPAR at 24-h post-sepsis diagnosis remained an independent S-AKI risk factor after adjusting for mechanical ventilation, blood urea nitrogen, and pH. Conclusions The findings suggest that plasma suPAR may be a potential biomarker for early S-AKI diagnosis.

Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study

BackgroundImproving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation.MethodsThis was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22–34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R–4.0.5).ResultsSuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19–51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27–84.16) vs. 20.46 ng/mL (IQR, 11.49–36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis.ConclusionSoluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) and graft-versus-host disease (GvHD) represent life-threatening syndromes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both conditions, endothelial dysfunction is a common denominator, and development of relevant biomarkers is of high importance for both diagnosis and prognosis. Despite the fact that soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings, their role in HSCT-related complications remains unexplored. In this context, we used immunoenzymatic methods to measure suPAR and GDF-15 levels in HSCT-TMA, acute and/or chronic GVHD, control HSCT recipients, and apparently healthy individuals of similar age and gender. We found considerably greater SuPAR and GDF-15 levels in HSCT-TMA and GVHD patients compared to allo-HSCT and healthy patients. Both GDF-15 and suPAR concentrations were linked to EASIX at day 100 and last follow-up. SuPAR was associated with creatinine and platelets at day 100 and last follow-up, while GDF-15 was associated only with platelets, suggesting that laboratory values do not drive EASIX. SuPAR, but not GDF-15, was related to soluble C5b-9 levels, a sign of increased HSCT-TMA risk. Our study shows for the first time that suPAR and GDF-15 indicate endothelial damage in allo-HSCT recipients. Rigorous validation of these biomarkers in many cohorts may provide utility for their usefulness in identifying and stratifying allo-HSCT recipients with endothelial cell impairment.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Leves Are Significantly Associated with Edothelial Injury Indices in Adult Allogenic Hematopoietic Cell Transplantation Recipients

Introduction: Endothelial dysfunction is a common denominator of graft-versus-host disease (GVHD) and transplant-associated thrombotic microangiopathy (TA-TMA). Among endothelial injury indices, the Endothelial Activation and Stress Index (EASIX) has been studied in allogeneic hematopoietic cell transplantation recipients (allo-HCT) recipients, while others including suPAR and GDF-15 have been determined only in other patient populations with hematologic diseases, such as in patients with Multiple Myeloma, AL- amyloidosis and Sickle Cell Disease. We hypothesized that suPAR and GDF-15 would reflect endothelial injury in allo-HCT recipients. Methods: We enrolled consecutive adult TA-TMA (classified according to current standardized criteria), acute and/or chronic graft-versus-host-disease (GVHD), control allogeneic hematopoietic cell transplantation (alloHCT) recipients and apparently healthy individuals of similar age and gender in a 1:1:1:1 ratio. Plasma was collected and stored immediately at -80 oC at the first day of confirmed TA-TMA or GVHD diagnosis and at a similar post-transplant period in control recipients. EASIX [lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10⁹ cells per L)] was calculated at day 0, 30, 100 and at last follow-up. Soluble C5b-9/membrane attack complex, suPAR and GDF-15 levels were measured using immunoenzymatic techniques. Results: We studied 20 TA-TMA, 20 GVHD, 20 control alloHCT patients, and 20 healthy controls. We found significantly higher suPAR and GDF-15 levels in TA-TMA and GVHD patients compared to alloHCT and healthy controls (p&amp;lt;0.001, Bonferroni's correction). Then, we further analyzed characteristics of the alloHCT population. TA-TMA developed at a median of 125 post-transplant day (range 9-2931); whereas the first day of confirmed GVHD diagnosis was at a median of 78 post-transplant day (range 16-145). Both GDF-15 and suPAR concentrations were associated with EASIX at day 100 (r=0.351, p=0.012 and r=0.338, p=0.015, respectively) and last follow-up (r=0.473, p&amp;lt;0.001 and r=0.410, p=0.020, respectively). Among the laboratory values used to calculate EASIX (LDH, creatinine, platelets), suPAR was associated with creatinine and platelets at day 100 and last follow-up; while GDF-15 only with platelets at both time points, suggesting that the association with EASIX is not driven by laboratory values per se. Interestingly, only suPAR and not GDF-15 levels was associated with soluble C5b-9 levels (p=0.013), a marker reflecting high risk in TA-TMA. Conclusion: Our study shows for the first time that suPAR and GDF-15 reflect endothelial injury in allo-HCT recipients. In accordance with other patient populations, suPAR emerges as a marker of renal dysfunction, characterizing high-risk in endothelial injury syndromes and in particular, TA-TMA. However, prior to their clinical usefulness, these biomarkers must undergo through rigorous validation in multiple cohorts.

Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated with Targeted Temperature Management.

Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log2 transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (pinteraction = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, p < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (plog-rank<0.05). The interaction of suPAR levels and TTH group was not significant (pinteraction = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (pinteraction = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.

SuPARnostic: an advanced predictive tool for detecting recurrence in renal cell carcinoma

BackgroundPlasma soluble urokinase-type Plasminogen Activator Receptor (suPAR) predicts disease aggressiveness in renal cell carcinoma (ccRCC), but its prognostic accuracy has not been investigated. To investigate the prognostic accuracy of preoperative plasma suPAR in patients who received curative treatment for initially localized ccRCC.MethodsWe retrospectively analyzed plasma samples stored in the Danish National Biobank between 2010 and 2015 from 235 patients with ccRCC at any stage. Relationships with outcome analyzed using univariate and multiple logistic Cox regression analysis.ResultsThere were 235 patients with ccRCC. The median follow-up period was 7.7 years. In univariate analysis suPAR ≥ 6 ng/mL was significantly associated with overall survival (OS) and recurrence-free survival (RFS). Patients with elevated suPAR were more likely to recur, with a Hazard Ratio (HR) of 2.3 for RFS. In multiple logistic regression, suPAR ≥ 6 ng/mL remained a negative predictor of OS and RFS. Limitations include retrospective study design, wide confidence intervals, and tumor subtype heterogeneity bias.ConclusionsccRCC patients with high plasma suPAR concentrations are at an elevated risk of disease recurrence and see lower OS. suPAR is a promising surveillance tool to more precisely follow up with ccRCC patients and detect future recurrences.Patient SummaryIn this study, we showed that new type of liquid marker in blood plasma, called suPAR, is associated to a higher risk of kidney cancer recurrence when elevated above 6ng/mL. We also showed suPAR to independently be able to predict patients overall and recurrence free survival in patient with any stage of kidney cancer.

The Relationship Between Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels and Treatment Response in Patients With Glomerulonephritis: A Single-Center Experience.

Aim Soluble urokinase-type plasminogen activator receptor (suPAR) is an important protein that is reported to increase in a broad range of inflammatory processes. We aimed to determine whether suPAR is a significant biomarker in glomerulonephritis for distinguishing patients with treatment response from patients without treatment response in our study. Materials and methods This was a prospective study in which 117 patients with biopsy-proven glomerulonephritis and 54 healthy individuals without a known chronic disease (control group) were enrolled. A total of 117 patients were divided into two groups: "treatment responsive" and "treatment nonresponsive." Blood samples were collected from the patients upon their outpatient clinic visits, and the demographical and lab parameters were compared between the groups. Results For the patient group consisting of 117 individuals, 56.4% were male, the mean age was 49.6 years, and the mean follow-up duration was 32.2 months. The most commonly diagnosed glomerular disease was focal segmental glomerulosclerosis (FSGS), followed by IgA nephropathy and membranoproliferative glomerulonephritis, respectively. While suPAR levels were significantly higher in the patient group (166.06 ± 127.66 vs. 119.67 ± 70.53 pg/ml, p = 0.001) (suPAR level± standard deviation), no significant relationship was found between suPAR levels, treatment response status, and disease severity. Besides, there was no significant relationship between suPAR levelsandproteinuria levels, BMI of the patients, and the type of immunosuppressive agent used in the treatment and BMI. Conclusion Our study showed that suPAR levels could distinguish a patient with glomerulonephritis from a healthy individual, whereas it has no value in predicting the disease progression and treatment responsiveness.

Diagnostic value of soluble urokinase-type plasminogen activator receptor in patients with acute coronary syndrome: A systematic review and meta-analysis.

In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS. A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed. Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001). In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.

#3647 RELATIONSHIP BETWEEN MONOCYTE-LYMPHOCYTE RATIO AND RENAL OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES

Abstract Background and Aims Acute kidney injury (AKI) is a common complication of hospitalized adults with increased risk of chronic kidney disease and end-stage kidney disease. Sepsis is the most common reason of AKI in patients admitted in intensive care unit(ICU) with the incidence over 50%. Soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator involved in kidney injury. Numerous studies have shown that the suPAR is associated with a variety of kidney diseases.However, it remains unknown on the diagnosis and prognosis value of suPAR in sepsis-associated acute kidney injury (S-AKI). Hence,this study aimed to explore the diagnostic value for the prediction of S-AKI courses and 28-day death. Method In this prospective study, adult patients with sepsis admitted to the ICU of Henan people's Hospital from December 2020 to February 2022 were enrolled. Plasma suPAR levels at 0, 12,24 and 48 hours after admission to ICU were measured by enzyme-linked immunosorbent assay. We assessed the development of S-AKI as the primary outcome and the occurrence of death within 28 days in patients who had S-AKI as a secondary outcome. The prediction of the suPAR level on S-AKI and death was tested using receiver operating characteristic curve (ROC) analysis, by calculating the area under the curve (AUC), and 95% confidence interval (CI). Results Of the 182 sepsis patients, 66 (36.3%) developed AKI during hospitalization, of whom 31 (46.9%) died. At 12,24 and 48 hours after admission to ICU, the plasma suPAR level was significantly higher in patients with S-AKI than in patients without AKI (P&amp;lt;0.05). (Fig. 1) In sepsis patients dead with 28 days after admission in ICU, the plasma suPAR level was significantly higher at 0 and 48 hours after admission in ICU compared to the survival patients(P&amp;lt;0.05). (Fig. 1) Diagnostic performance of plasma suPAR level improved over time with the highest area under the receiver operating characteristic curve of 0.701 (95% CI, 0.623∼0.779) 24 hours after study inclusion. Additionally, plasma suPAR levels at 0h have the highest area under the receiver operating characteristic curve of 0.647 (95% CI, 0.512∼0.782) in predicting 28-day death. The best discrimination ability for the S-AKI was achieved for suPAR 24 hours after inclusion by applying a cutoff value of greater than or equal to 6.31 ng/ml (sensitivity 62.1, specificity 71.6). The suPAR at 0h after inclusion performed best in discriminating 28-day death by using a cutoff value of greater than or equal to 4.57 ng/mL (sensitivity 87.1, specificity 51.4).(Table 1) Conclusion Plasma suPAR level can be a potential biomarker for early diagnosis of S-AKI and has a certain clinical value in predicting the short-term death of S-AKI. However, further clinical studies with larger sample size is needed.

#3644 CLINICAL VALUE OF SOLUBLE UROKINASE-TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN DIAGNOSIS AND PROGNOSIS OF SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) is a common complication of hospitalized adults with increased risk of chronic kidney disease and end-stage kidney disease. Sepsis is the most common reason of AKI in patients admitted in intensive care unit(ICU) with the incidence over 50%. Soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator involved in kidney injury. Numerous studies have shown that the suPAR is associated with a variety of kidney diseases.However, it remains unknown on the diagnosis and prognosis value of suPAR in sepsis-associated acute kidney injury (S-AKI). Hence,this study aimed to explore the diagnostic value for the prediction of S-AKI courses and 28-day death. Method In this prospective study, adult patients with sepsis admitted to the ICU of Henan people's Hospital from December 2020 to February 2022 were enrolled. Plasma suPAR levels at 0, 12,24 and 48 hours after admission to ICU were measured by enzyme-linked immunosorbent assay. We assessed the development of S-AKI as the primary outcome and the occurrence of death within 28 days in patients who had S-AKI as a secondary outcome. The prediction of the suPAR level on S-AKI and death was tested using receiver operating characteristic curve (ROC) analysis, by calculating the area under the curve (AUC), and 95% confidence interval (CI). Results Of the 182 sepsis patients, 66 (36.3%) developed AKI during hospitalization, of whom 31 (46.9%) died. At 12,24 and 48 hours after admission to ICU, the plasma suPAR level was significantly higher in patients with S-AKI than in patients without AKI (P&amp;lt;0.05). (Figue 1) In sepsis patients dead with 28 days after admission in ICU, the plasma suPAR level was significantly higher at 0 and 48 hours after admission in ICU compared to the survival patients(P&amp;lt;0.05). (Figue 1) Diagnostic performance of plasma suPAR level improved over time with the highest area under the receiver operating characteristic curve of 0.701 (95% CI, 0.623∼0.779) 24 hours after study inclusion. Additionally, plasma suPAR levels at 0h have the highest area under the receiver operating characteristic curve of 0.647 (95% CI, 0.512∼0.782) in predicting 28-day death. The best discrimination ability for the S-AKI was achieved for suPAR 24 hours after inclusion by applying a cutoff value of greater than or equal to 6.31 ng/ml (sensitivity 62.1, specificity 71.6). The suPAR at 0h after inclusion performed best in discriminating 28-day death by using a cutoff value of greater than or equal to 4.57 ng/mL (sensitivity 87.1, specificity 51.4). (Table 1) Conclusion Plasma suPAR level can be a potential biomarker for early diagnosis of S-AKI and has a certain clinical value in predicting the short-term death of S-AKI. However, further clinical studies with larger sample size is needed.

Soluble urokinase-type plasminogen activator receptor, suPAR, as a prognostic biomarker in advanced pancreatic cancer.

e16277 Background: High levels of intact and cleaved forms of the urokinase-type Plasminogen Activator Receptor (uPAR) in tissue and blood are associated with a poor prognosis in several types of cancer, including lung, colon, bladder, and cholangiocarcinoma. The soluble forms of uPAR (suPAR) have not been investigated in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to determine if circulating levels of intact and cleaved suPAR were associated with overall survival (OS) in patients with advanced PDAC. Methods: Patients with PDAC stage 3 or 4 were consecutively included in the BIOPAC study (ClinicalTrials.gov ID: NCT03311776) in a training cohort (n = 230, age 45-89 years, 56% females) from Herlev Hospital and a validation cohort (n = 115, age 40-82 years, 59% females) from four other Danish hospitals between 2008 to 2014. A total of 95% of the patients in the training cohort and 93% in the validation cohort received first-line palliative chemotherapy. One patient was alive at the time of analysis at 8 years follow-up. Serum samples were collected prior to palliative chemotherapy. Different suPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for uni- and multivariate analyses. Age, performance status, stage (4 vs 3), gender, Charlson age-adjusted comorbidity index, and CA19-9 were included in the multivariate analysis for OS. Results: In the training cohort, high level of suPAR domain I was an independent biomarker of short OS (HR, 1.37, 95% CI 1.15-1.63, p = 0.0004). High CA19-9 (HR, 1.08, 95% CI 1.04-1.12, p &lt; 0.0001), PS, and stage were also independent prognostic parameters in the training cohort. In the validation cohort, high level of suPAR domain I (HR, 1.91, 95% CI 1.36-2.69, p = 0.0002) and CA 19-9 (HR, 1.09, 95% CI 1.01-1.17, p = 0.02) were confirmed as independent prognostic biomarkers for short OS. No correlation was observed between suPAR domain 1 and CA19-9 (r = 0.059, p = 0.21). Conclusions: A high pretreatment circulating level of suPAR domain I is associated with a short OS in patients with advanced PDAC, and the biomarker is independent of CA19-9. The results warrant further investigation of suPAR domain 1 as a biomarker in patients with PDAC.

Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors.

Focal segmental glomerulosclerosis (FSGS) is frequently associated with heavy proteinuria and progressive renal failure requiring dialysis or kidney transplantation. However, primary FSGS also has a ~40% risk of recurrence of disease in the transplanted kidney (rFSGS). Multiple circulating factors have been identified to contribute to the pathogenesis of primary and rFSGS including soluble urokinase-type plasminogen activator receptor (suPAR) and patient-derived CD40 autoantibody (CD40autoAb). However, the downstream effector pathways specific to individual factors require further study. The tumor necrosis factor, TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS has been supported by multiple studies. A human in vitro model was used to study podocyte injury measured as the loss of actin stress fibers. Anti-CD40 autoantibody was isolated from FSGS patients (recurrent and non-recurrent) and control patients with ESRD due to non-FSGS related causes. Two novel human antibodies-anti-uPAR (2G10) and anti-CD40 antibody (Bristol Meyer Squibb, 986090) were tested for their ability to rescue podocyte injury. Podocytes treated with patient derived antibody were transcriptionally profiled using whole human genome microarray. Here we show that podocyte injury caused by sera from FSGS patients is mediated by CD40 and suPAR and can be blocked by human anti-uPAR and anti-CD40 antibodies. Transcriptomic studies to compare the molecules and pathways activated in response to CD40 autoantibody from rFSGS patients (rFSGS/CD40autoAb) and suPAR, identified unique inflammatory pathways associated with FSGS injury. We identified several novel and previously described genes associated with FSGS progression. Targeted blockade of suPAR and CD40 pathways with novel human antibodies showed inhibition of podocyte injury in FSGS.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Is a Biomarker Associated with Left Ventricular Hypertrophy in the Elderly, Specifically in Women.

Left ventricular hypertrophy (LVH) may result in the development of heart failure, which is widespread among people of advanced age. The pathophysiology of LVH is complex and its biochemical pathways are not fully understood in this group. Elevated soluble urokinase-type plasminogen activator receptor (suPAR), a biomarker of immune activation, including fibrosis, reflects subclinical organ damage in systematic diseases. The present study assesses the clinical role of suPAR measurement in determination of LVH-associated cardiac disorders in the elderly. The studied population consisted of 238 individuals aged 76-91 years; of these, 139 (58%) were diagnosed with LVH. Serum biomarkers measurement (suPAR, troponin T, NT-proBNP and CRP) and echocardiography were performed in all subjects. The suPAR level was significantly higher in the LVH group (4.01 vs. 3.82 ng/mL, p = 0.033) and correlated with the parameters of cardiac diastolic function. Stepwise logistic regression found suPAR level (OR = 1.55, p = 0.016), BMI (OR = 1.17, p = 0.0003) and hypertension (OR = 2.42, p = 0.046) to be independently associated with LVH in women. In men, the strongest predictors of LVH were hypertension (OR = 7.52, p = 0.014) and BMI (OR = 1.42, p = 0.032). The observations indicate suPAR as a promising marker reflecting LVH, especially in women at advanced age, independent of age-associated cardiac remodeling.

Soluble urokinase-type plasminogen activator receptor in sickle cell disease-associated chronic kidney disease.

Soluble urokinase-type plasminogen activator receptor in sickle cell disease-associated chronic kidney disease.

The accuracy of soluble urokinase-type plasminogen activator receptor for the diagnosis of neonatal sepsis: a meta-analysis.

Neonatal sepsis is one of the major causes of morbidity and mortality in newborns. However, atypical clinical manifestations and symptoms make the early diagnosis of neonatal sepsis a challenge. Relatively high-serum soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated as a diagnostic biomarker for adult sepsis. Therefore, the meta-analysis is intended to explore the diagnostic value of suPAR for neonatal sepsis. The PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Biological Medicine Disk, and Wanfang databases were retrieved from inception to 31 December 2022 to collect diagnostic accuracy studies about suPAR for neonatal sepsis. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool. Then, a meta-analysis was performed using Stata 15.0 software. A total of six articles involving eight studies were included. The results of the meta-analysis showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.89 [95%CI (0.83-0.93)], 0.94 [95%CI (0.77-0.98)], 14 [95%CI (3.5-55.2)], 0.12 [95%CI (0.08-0.18)], and 117 [95%CI (24-567)], respectively. The area under the curve (AUC) of summary receiver operator characteristic (SROC) curves was 0.92 [95%CI (0.90-0.94)]. Sensitivity analysis confirmed the stability of the results, and publication bias was not observed. Fagan's nomogram results demonstrated the clinical availability of the findings. Current evidence suggests that suPAR has potential diagnostic value for neonatal sepsis. Owing to the limited quality of the included studies, more high-quality studies are needed to verify the above conclusion.