Search

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. 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. 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. The findings suggest that plasma suPAR may be a potential biomarker for early S-AKI diagnosis. [ABSTRACT FROM AUTHOR]

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) is a circulating protein that has been found to be a promising biomarker for a variety of kidney injuries. The predictive utility of suPAR in contrast-induced acute kidney damage (CI-AKI) in percutaneous coronary intervention (PCI) is uncertain. Aim: This study aimed to assess the prediction of CI-AKI using suPAR in patients undergoing PCI. Methods: This case-control study was carried out on 80 subjects undergoing PCI. The subjects were divided into two groups. Forty patients developed CIAKI, in addition to the control group, which included 40 subjects with non-CI-AKI. The radial or right femoral artery was punctured using the PCI Seldinger puncture technique. A specific laboratory investigation was the evaluation of suPAR in serum using the Luminex assay. Results: The suPAR marker was a significant predictor of CI-AKI among PCI patients (AUC=0.982, P<0.001). The suPAR cutoff point (>2.55 ng/mL) showed a sensitivity of 92.5% and a specificity of 97.5% for the diagnosis of CI-AKI. Combined creatinine before contrast and suPAR cutoff points showed a sensitivity of 95% and a specificity of 100%. In CI-AKI patients, there was a significant positive correlation between suPAR marker levels and each creatinine level after contrast (r=0.375, P=0.017) and urinary albumin creatinine ratio (r=0.396, P=0.011). Increased levels of suPAR were associated with higher odds for having CI-AKI (OR 2334.63). Conclusions: Higher suPAR levels were detected in cases in comparison to controls. SuPAR showed accepted performance criteria in CI-AKI prediction. The combined creatinine level before contrast and suPAR improves the sensitivity and specificity. The suPAR seems to be a predictor of CI-AKI in primary PCI. [ABSTRACT FROM AUTHOR]

Fetal inflammatory response syndrome or infection after preterm premature rupture of membranes (PPROM) increases neonatal morbidity in preterm deliveries. Biochemical markers from the amniotic fluid (AF) have been used to evaluate possible intra-amniotic infection during the asymptomatic phase after PPROM. This study aimed to describe whether soluble urokinase-type plasminogen activator receptor (suPAR) or procalcitonin (PCT) from AF or maternal sera could reveal fetal inflammatory response or infection after PPROM. AF and maternal serum samples were collected weekly after PPROM (23+ 0 − 34+ 6 gestational weeks) until delivery from twenty women and two women with possible chorioamnionitis with intact membranes. Levels of suPAR, PCT, interleukin-6 (IL-6), glucose, lactate dehydrogenase (LDH), and bacterial PCR were determined from AF and suPAR and PCT and IL-6 from maternal sera. Fetal infection or inflammation response were determined by the histology of the placenta after delivery. AF glucose was significantly lower and AF LDH higher in the fetal site histologic chorioamnionitis (HCA) group, while AF suPAR concentrations tended to be higher in this group. AF suPAR correlated significantly with AF glucose and LDH. Based on receiver operating characteristic (ROC) analysis, AF glucose had the best predictability for fetal site histological chorioamnionitis. The findings of AF PCT were insignificant considering HCA. AF glucose had the highest accuracy in predicting fetal site histologic chorioamnionitis. AF suPAR may be a promising marker; however, our findings were limited by a small study population. [ABSTRACT FROM AUTHOR]

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

BackgroundFocal 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.MethodsA 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.ResultsHere 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.ConclusionsWe 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.

Background: Urinary tract infections (UTIs) are a leading bacterial infection in the emergency department (ED). Diagnosing UTIs in the ED can be challenging due to the heterogeneous presentation; therefore, fast and precise tests are needed. We aimed to evaluate the diagnostic precision of procalcitonin (PCT), soluble urokinase plasminogen activator receptors (suPARs), and C-reactive protein (CRP) in diagnosing UTIs, grading the severity of UTIs, and ruling out bacteremia. Methods: We recruited adults admitted to three Danish EDs with suspected UTIs. PCT, suPAR, and CRP were used in index tests, while blood cultures, expert panel diagnosis, and severity grading were used in the reference tests. Logistic regression and area under the receiver operator characteristic curves (AUROCs) were utilized to evaluate the models and determine the optimal cut-offs. Results: We enrolled 229 patients. PCT diagnosed UTI with an AUROC of 0.612, detected severe disease with an AUROC of 0.712, and ruled out bacteremia with an AUROC of 0.777. SuPAR had AUROCs of 0.480, 0.638, and 0.605, while CRP had AUROCs of 0.599, 0.778, and 0.646. Conclusions: The diagnostic performance of PCT, suPAR, or CRP for UTIs or to rule out severe disease was poor. However, PCT can safely rule out bacteremia in clinically relevant numbers in ED patients suspected of UTI. [ABSTRACT FROM AUTHOR]

Background: Sepsis is one of the main causes of morbidity and mortality in the intensive care units (ICUs). It is difficult to differentiate it accurately and timely from other confusing conditions. So, it is of utmost importance to evaluate new biomarkers with a differentiation ability between sepsis and nonsepsis conditions. Soluble urokinase-type plasminogen activator receptor (suPAR) is a stable biomarker of inflammation. The aim of the study is to evaluate the value of suPAR in the diagnosis of septic ICU patients and to compare it (if present) with that of Creactive protein (CRP) and procalcitonin (PCT). Methods: A case-control study was conducted at Zagazig University Hospitals from December 2017 to October 2019. A total of 90 subjects were enrolled in the study. Based on Systemic Inflammatory Response Syndrome (SIRS) criteria, they were divided into 2 groups: (i)Group A: 60 septic ICU admitted patients;(ii)Group B: 30 non-septic ICU admitted patients as control group. Single determination of level of serum suPAR was measured by enzyme-linked immunosorbent assay (ELISA) for all the participants. Results: Septic ICU patients had statistically significant higher serum suPAR, CRP and PCT levels than non-septic patients. suPAR had a sensitivity of 72%, specificity of 70% and AUC of 0.7 in sepsis diagnosis. Conclusion: Serum suPAR is a fair diagnostic test for septic ICU patients at cut-off 3.983 ng/ml but does not surpass that of PCT or CRP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundNeonatal 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.MethodsThe 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.ResultsA 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.ConclusionCurrent 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.

Cardiovascular diseases (CVDs) remain a significant cause of death in hemodialysis (HD) patients. To explore their associations, we examine the role of soluble urokinase-type plasminogen activator receptor (suPAR) in arterial stiffness in chronic HD patients. From June to August 2020, we recruited 135 chronic HD patients. The arterial stiffness group included patients with a carotid–femoral pulse-wave velocity (cfPWV) of >10 m/s. Fifty-five HD patients (40.7%) were in the arterial stiffness group. They had a higher prevalence of diabetes (p = 0.001) and hypertension (p = 0.039), were older (p = 0.007) and had higher aortic systolic blood pressure (p = 0.034), brachial systolic blood pressure (p = 0.025), glucose (p = 0.019), C-reactive protein (p = 0.039), and AIx75 (p = 0.003) and suPAR (p < 0.001) levels than the control group. After we performed multivariable logistic regression analysis, except age and glucose, serum suPAR (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.48–2.70, p < 0.001) was independently associated with arterial stiffness in chronic HD patients. In the multivariable linear regression analysis, suPAR positively correlated with cfPWV (β = 0.475, p < 0.001) and could serve as a biomarker for arterial stiffness development in patients undergoing HD. [ABSTRACT FROM AUTHOR]

Background Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria. Methods Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]). Results Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P <.0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P =.001; 1 vs 2, P <.001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P <.0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI},.91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI,.91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI,.96–.98]; P <.0001). Conclusions Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials. [ABSTRACT FROM AUTHOR]

Background: Some clinical trials have shown that soluble urokinase-type plasminogen activator receptor (suPAR) has good predictive value for acute kidney injury (AKI), but there is still a lack of evidence-based proof. Therefore, we conducted this systematic review and meta-analysis to evaluate the predictive value of suPAR for AKI. Methods: Pubmed, EMBASE, Cochrane Library, and Web of Science databases were searched until December 2021 to obtain the literature on the prediction of suPAR for AKI. The quality of the included studies was assessed using the QUADAS-2 scoring system, and a bivariate random-effect model was used for the meta-analysis. The present study has been registered on PROSPERO (Registration No. CRD42022324978). Results: Seven articles were included, involving 2,319 patients, 635 of whom were AKI patients. The meta-analysis results showed that the combined sensitivity of suPAR in predicting AKI was 0.77 (95% CI 0.67–0.84); the specificity was 0.64 (95% CI 0.53–0.75); the odds ratio of diagnosis was 6 (95% CI 3–10); the pooled positive likelihood ratio was 2.2 (95% CI 1.6–2.9); the pooled negative likelihood ratio was 0.36 (95% CI 0.26–0.52); and the area under the summary receiver-operating characteristic (SROC) curve was 0.77 (95% CI 0.12~0.99). Deek's funnel plot suggested no potential publication bias among included studies. Conclusion: suPAR is a valuable biomarker for the prediction of AKI with relatively high predictive accuracy, but its clinical application needs improvements. SuPAR should be considered as an indicator in the subsequent development of more effective predictive tools for AKI. [ABSTRACT FROM AUTHOR]

Background: Inflammation is a common feature of many kidney diseases. The implicated inflammatory mediators and their underlying molecular mechanisms however are often not clear. Summary: suPAR is the soluble form of urokinase-type plasminogen activator receptor (uPAR), associated with inflammation and immune activation. It has evolved into a unique circulating kidney disease factor over the last 10 years. In particular, suPAR has multiple looks due to enzymatic cleavage and alternative transcriptional splicing of the uPAR gene. Most recently, suPAR has emerged as a systemic mediator for COVID-19 infection, associated with lung as well as kidney dysfunction. Like membrane-bound uPAR, suPAR could interact with integrins (e.g., αvβ3 integrin) on podocytes, providing the molecular basis for some glomerular kidney diseases. In addition, there have been numerous studies suggesting that suPAR connects acute kidney injury to chronic kidney disease as a special kidney risk factor. Moreover, the implication of circulating suPAR levels in kidney transplantation and plasmapheresis not only indicates its relevance in monitoring for recurrence but also implies suPAR as a possible therapeutic target. In fact, the therapeutic concept of manipulating suPAR function has been evidenced in several kidney disease experimental models. Key Messages: The last 10 years of research has established suPAR as a unique inflammatory mediator for kidneys. While open questions remain and deserve additional studies, modulating suPAR function may represent a promising novel therapeutic strategy for kidney disease.

Herein, host–guest ligand-assembled gold nanoclusters (AuNCs) with highly efficient electrochemiluminescence (ECL) as an emitter and a programable tripedal deoxyribonucleic acid (DNA) walker with a well-regulated DNA track as the signal amplifier were used to develop an ultrasensitive biosensing platform for determining soluble urokinase-type plasminogen activator receptor (suPAR) related to chronic kidney disease. Notably, the host–guest ligand-assembled AuNCs with 6-aza-2-thiothymine (ATT) as the ligand and guanidine butyric acid (Gba) as the model (Gba/ATT-AuNCs) exhibited a strong and stable ECL signal under preoxidation, 25.6 times higher than that of traditional ATT-protected AuNCs (ATT-AuNCs). This is because of the dual-enhancement ECL mechanism of the suppression of nonradiative transitions by host–guest recognition and the improvement of the electrochemical redox rate by preoxidation. Furthermore, the trace target protein suPAR could be efficiently converted into a tripedal DNA walker to walk along a well-regulated square DNA orbit with high movement efficiency and low background signal, thereby considerably improving detection sensitivity. Thus, the established ECL sensing platform achieved the ultrasensitive detection of suPAR with a linear range from 10 fg/mL to 10 ng/mL and a limit of detection of 3.15 fg/mL, whose detection sensitivity was five orders of magnitude higher than that of the gold-standard enzyme-linked immunosorbent assay with the lowest detection concentration of 1 ng/mL. This strategy provides a novel enhanced ECL mode of AuNCs for constructing a sensitive biosensing platform and is expected to be extended to the trace detection of other protein markers in human body fluids for disease diagnosis. • The Gba/ATT-AuNCs exhibited a strong and stable ECL signal via dual enhancement ECL path. • An ECL biosensor was designed to detect suPAR related to chronic nephritis disease. • The sensitivity was five orders of magnitude higher than that of the ELISA. [ABSTRACT FROM AUTHOR]

Objective To explore the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) for severe acute pancreatitis (SAP). Methods A prospective cohort study was designed to enroll 103 patients with acute pancreatitis who were admitted to our department from March 1 to June 1, 2021, including 23 SAP and 80 non-severe acute pancreatitis (NSAP). Another 30 healthy subjects were recruited concurrently as control group. The plasma samples of all subjects were collected on the first day of admission to detect the level of suPAR using ELISA. General clinical data and the levels of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer and serum calcium (Ca2+), as well as the results of blood routine and biochemical examinations of patients were all collected. Acute Physiology and Chronic Health Evaluation (APACHEⅡ) score and Ranson's score were subsequently calculated. For the control subjects, only their demographic characteristics (age and gender) were collected. Statistical analysis was adopted on the above data. Results The plasma suPAR level was significantly higher in the patients with NSAP and SAP than the control group (P < 0.05), and also notably higher in those of the SAP group than those out of the NSAP patients (P < 0.05). Pearson correlation analysis showed that plasma suPAR level was positively correlated with both APACHE Ⅱ score and Ranson's score (R=0.554, R=0.485, P < 0.05). Multivariate Logistic regression analysis indicated that suPAR, D-dimer and Ca2+ levels were independent predictors of SAP. ROC curve demonstrated that serum suPAR had a good predictive value for SAP (AUC=0.869). Conclusion The plasma level of suPAR is closely correlated with the severity of acute pancreatitis, and plays an important role in prediction of SAP.

Background: A potential inflammatory biomarker, soluble urokinase‐type plasminogen activator receptor (suPAR) has been utilized to assist the prognostic assessment of coronary artery disease (CAD) patients; however, outcomes have been inconsistent. The prognostic relevance of suPAR as a predictor of CAD patient adverse outcomes was therefore examined. Methods: Research articles published as of 1 January 2022 were retrieved from PubMed, Embase, the Web of Science and the Cochrane Library. All‐cause mortality, cardiovascular mortality and other major cardiovascular events (nonfatal myocardial infarction, heart failure or stroke) were analysed as a subset of relevant studies' results. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each study. The broad EQUATOR guidelines were conformed. Risk of bias was assessed with ROBINS‐I tool. Results: In total, this analysis included nine studies including 14,738 CAD patients. All included studies made a correction for certain potential confounders. However, risk of bias ranged from moderate to critical. When the ROBINS‐I tool was used. Patients with CAD that exhibited increased suPAR levels had a substantially higher risk of all‐cause mortality (HR = 2.24; 95% CI 1.97–2.55) or cardiovascular mortality (HR = 2.02; 95% CI 1.58–2.58), but not of developing other major cardiovascular events (HR = 1.63; 95% CI 0.86–3.11). Considerable heterogeneity across studies was observed in our meta‐analyses, but no significant publication bias was detected. Conclusion: In patients with coronary disease, suPAR may have prognostic value for both all‐cause and cardiovascular mortality but not for other major cardiovascular events. [ABSTRACT FROM AUTHOR]

Yuhan Qin, Yong Qiao, Dong Wang, Gaoliang Yan, Chengchun Tang, Genshan Ma Department of Cardiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Gaoliang YanDepartment of Cardiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaEmail yan_seu@hotmail.comObjective: Soluble urokinase-type plasminogen activator receptor (SuPAR) is a circulating protein and a novel identified promising biomarker for various renal diseases and kidney injury. However, it remains unknown on the predictive value of suPAR in contrast induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI).Methods: A total of 399 patients undergoing PCI were enrolled in the research from June 2020 to June 2021 in Zhongda Hospital. Patients were divided into CI-AKI and non-CI-AKI groups according to the preoperative and postoperative serum creatinine levels. Plasma suPAR level was detected through enzyme-linked immunosorbent assay on admission. Demographic data, hematological parameters, coronary angiography data and medications were recorded and compared between CI-AKI and non-CI-AKI groups. Logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed for identifying the independent risk factors of CI-AKI and assessment of the predictive value of suPAR for CI-AKI.Results: CI-AKI occurred in 65 (16.3%) patients undergoing PCI. The level of suPAR in CI-AKI group was significantly higher than that in the non-CI-AKI group. Multivariate logistic regression indicated diabetes, lower LVEF, lower hydration rate, lower baseline eGFR, higher plasma suPAR (OR = 2.875, 95% CI = 2.038– 3.672, P < 0.001) and volume of contrast media were all independent risk factors for CI-AKI after adjustment of the confounding factors. ROC analysis illustrated that the optimal area under the curve was 0.765, indicating plasma suPAR was a splendid predictor for CI-AKI. The corresponding cut-off value was 3.305 ng/mL, and the sensitivity and specificity were 63.1% and 82.3%, respectively.Conclusion: Increased suPAR level is independently associated with elevated risk of suffering CI-AKI, and suPAR is a strong predictor for CI-AKI in patients undergoing PCI. SuPAR might act as a novel biomarker for CI-AKI in clinical practice.Keywords: soluble urokinase-type plasminogen activator receptor, contrast media, acute kidney injury, percutaneous coronary intervention

Background: To explore the values of serum procalcitonin (PCT), soluble urokinase-type plasminogen activator receptor (suPAR) combined with APACHE II and SOFA scores for evaluating the prognosis of septic shock patients.

Objective To investigate the predictive value of plasma soluble urokinase-type plasminogen activator receptor (suPAR) for post-severe traumatic multiple organ dysfunction syndrome (MODS). Methods A total of 108 patients suffering from severe trauma admitted to the Trauma Center of our hospital from December 2019 to December 2020 were enrolled. Venous blood samples were collected at admission and plasma suPAR concentration was measured by ELISA, and their demographic and clinical data were collected. The patients were divided into MODS group and non-MODS group according to the sequential organ failure assessment(SOFA) within 14 d after admission. The general data and variables such as suPAR, white blood cell (WBC) count, and injury severity score (ISS) were compared between the 2 groups. Logistic regression analysis was used to screen the independent predictors for post-traumatic MODS, and receiver operating characteristic (ROC) curve was adopted to evaluate the predictive value of the variables. Results Age, rate of comorbidity, ISS, suPAR at admission, rate of shock, rate of infection and rate of surgery were significantly higher in the MODS group than the non-MODS group [52.6±14.1 vs 46.1±14.1 years old, 29.4% vs 9.5%, 29 (25, 33) vs 26 (21, 30) points, 6.7±2.7 vs 5.0±2.1 ng/mL, 41.2% vs 17.6%, 61.8% vs 24.3%, 52.9% vs 32.4%, P < 0.05]. There were no significant differences in sex, injury cause, injury site, WBC count, and rate of blood purification between the 2 groups. Multivariate Logistic regression analysis showed that comorbidity, ISS, suPAR, and infection were independent predictors for post-traumatic MODS (P < 0.05). ROC curve analysis indicated that the area under the curve (AUC) of suPAR for predicting post-traumatic MODS was 0.704 (P < 0.05). When the cutoff value was 5.04 ng/mL, the sensitivity was 73.5% and the specificity was 62.2%. The AUC of ISS was 0.632 (P < 0.05), and the sensitivity was 73.5% and the specificity was 58.1% when the cutoff value was 26. Conclusion The plasma suPAR level at admission can predict the occurrence of post-traumatic MODS in patients with severe trauma. Early monitoring of suPAR has a certain value in evaluation of inflammation and immune activation in the body and in guidance of clinical evaluation and treatment.

To determine the prognostic performance of soluble urokinase-type plasminogen activator receptor (suPAR) and quick Sequential Organ Failure Assessment (qSOFA) in predicting the 28-day mortality of sepsis patients admitted to the emergency department (ED). A prospective, single-center observational study was conducted between June 2018 and June 2019. In total, 175 patients with sepsis and septic shock admitted to the ED were enrolled based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). We assessed the qSOFA score on ED admission and measured serum suPAR levels by quantitative enzyme-linked immunosorbent assay. Univariate and multivariate analysis was performed to identify predictors of prognosis. Kaplan-Meier survival curves and areas under the receiver operating characteristic (ROC) curve for 28-day mortality were calculated. We estimated category-free net reclassification improvement (NRI) when suPAR was added to qSOFA. Increased suPAR levels were significantly associated with 28-day mortality [1.74 (1.24-2.51) ng/mL in survivors vs. 1.34 (0.96-2.00) ng/mL in non-survivors, p = 0.011] and with sepsis severity [1.34 (0.991.98) ng/mL in sepsis vs. 1.74 (1.22-2.65) ng/mL in septic shock, p = 0.039]. The area under the curve (AUC) for the prediction of 28-day mortality was 0.646 (95% confidence interval (CI): 0.553-0.740) for suPAR, 0.832 (95% CI: 0.692-0.923) for qSOFA and 0.864 (95% CI: 0.802-0.928) for combined suPAR and qSOFA. Serum suPAR did not significantly increase the AUC of the basic qSOFA, but a model containing suPAR and qSOFA had a continuous NRI of 11% (95% CI: 3.5-18.5%; p = 0.004). Serum suPAR was associated with sepsis severity and 28-day mortality. Adding suPAR to qSOFA increased the ROC curve area and improved its discrimination, suggesting that this might be a useful tool in sepsis mortality prediction models. [ABSTRACT FROM AUTHOR]

Background Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. Methods We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. Results In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. Conclusion In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.

Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR. [ABSTRACT FROM AUTHOR]

Background Soluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P=0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P=0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P=0.03) with every 1‐unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

Featured Application: The presented study opens the way for the inclusion of suPAR in the maxillofacial diagnostics. The study aims to predict the possibility of minor inflammatory complications after maxillofacial scheduled procedures to a population of potentially healthy patients as far as internal diseases are considered. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of immune activation and reflects a more distinct aspect of inflammation than C-reactive protein (CRP) does. The study concerns a clinically silent state of the immune system expressed by the level of suPAR, which could affect the occurrence of complications (non-life threatening) after scheduled procedures. The purpose was the evaluation of suPAR predictive value in minor maxillofacial surgery complication incidents. Eighty patients were tested for suPAR, CRP and a series of basic laboratory serum tests on 1 day before surgery. Complications of orthognathic and minor injuries treatments were reported. The suPAR level, expressed as a measure independent of the patient's age (Index of Body Inflammation, IBI), was analyzed. The protein level was also assessed on postoperative day 3. Basic statistical analysis did not reveal any relevant dependence between suPAR (or IBI) and occurrence of minor complications. The application of factor analysis, artificial neural network and inclusion of chlorides, glycaemia, alanine transaminase (ALT), albumin and hemoglobin levels allowed to indicate the suPAR/IBI ranges associated with an increased risk of minor postoperative complications. Concluding, it seems that, in the current state of the knowledge, the monitoring of pre-operational suPAR level solely does not include sufficient predictive information for the occurrence of minor complications after maxillofacial surgery. The suPAR/IBI level should be combined with other patient characteristics to predict healing complications. [ABSTRACT FROM AUTHOR]

Featured Application: Inflammation is still a threat to patients of all age groups. Monitoring the infection is essential to control it. The soluble urokinase-type plasminogen activator receptor (suPAR) is a very sensitive marker. Maxillofacial surgery is one of the fields of medicine widely fighting against infections. The concentration of suPAR holds an independent information for risk stratification of morbidity and mortality in various acute and chronic diseases. The use of an ultra-sensitive measure of the development of inflammation and at the same time independent on the patient's age would be clinically very beneficial. Background: The serum suPAR level is affected in humans by it increases with age. Therefore it makes difficult interpretation and any comparison of age varied groups. The aim of this study is to find simple way to age independent presentation of suPAR serum level for maxillofacial surgery purpose. Methods: In generally healthy patients from 15 to 59 y.o. suPAR level was tested in serum before orthognathic or minor traumatologic procedures. Five ways to make the suPAR serum level assessment independent of age are proposed. Results: One way of making suPAR levels independent of age led to the result with the same statistical distribution as in the raw suPAR serum material and this distribution is the normal. Conclusion: The simple way for suPAR serum level analysis without its dependence on patient age is calculation of the index of body inflammation understood as square root of squared suPAR serum level divided by logarithm of patient age to base 10. [ABSTRACT FROM AUTHOR]

Objective: Acute pancreatitis (AP) is an inflammatory disease in which digestive enzymes produced by pancreas destroy the gland via protease pancreatic autodigestion. Soluble urokinase-type plasminogen activator receptor (suPAR), an inflammatory biomarker, is responsible for various immunological functions, including inflammation, cell adhesion, migration and proteolysis. The main goal of our study was to evaluate serum suPAR level in patients with mild AP, compared with controls. Material and Method: The study was performed on 40 patients with mild AP and 50 healthy controls. Controls were matched with patients as to age and body mass index (BMl). The diagnosis of AP was established under the Ranson criteria. Serum suPAR levels were measured through ELISA method. Results: Serum suPAR levels of patients were significantly higher than those of control subjects (4.81±3.30; 1.98+1.78 ng/ml, respectively) (pcO.OOl). No significant correlation was found between suPAR levels, amylase, lipase, CRP, hs-CRP and fibrinogen levels (p>0.05for all parameters). Conclusion: Our study indicated that serum suPAR may play an important role in the inflammatory process in AP, and suPAR could be used as a clinically beneficial marker in the diagnosis of AP. [ABSTRACT FROM AUTHOR]

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase‐type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography—including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow‐up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P

Abstract Background Soluble urokinase-type plasminogen activator receptor (suPAR) has emerged as a new sepsis biomarker. It is not known whether suPAR has a role in critically ill patients with severe acute kidney injury (AKI). Methods Our main aims were to describe serial serum suPAR concentrations in patients with severe AKI, to investigate a potential association between suPAR and C-reactive protein (CRP), and to compare suPAR and CRP as diagnostic markers of infection in patients with AKI. Between April 2013 – April 2014, we recruited adult patients (≥18 years) with AKI KDIGO stage 2/3 admitted to a multidisciplinary Intensive Care Unit (ICU) in a University Hospital in UK. Serial serum suPAR and CRP concentrations were measured for 6 days. We compared the characteristics and serial suPAR and CRP concentrations of patients with and without an infection using Chi-squared, Fisher’s exact, t-test and Mann-Whitney tests as appropriate, and calculated the area under the receiver operating characteristics curve (AUC). Results Data of 55 patients with AKI stage 2/3 were analysed (62% male; mean age 60.5) of whom 43 patients received continuous renal replacement therapy. suPAR was not detectable in effluent fluid. There was no significant correlation between daily suPAR and CRP concentrations. In patients with an infection, suPAR results were significantly higher than in those without an infection across all time points; there was no significant difference in CRP levels between both groups. After exclusion of patients with an infection before or on day of admission to ICU, the AUC of suPAR for predicting an infection later was 0.62 (95% CI 0.43–0.80) compared to 0.50 (95% CI 0.29–0.71) for CRP. Conclusions In critically ill patients with AKI stage 2/3, suPAR is a better marker of infection than CRP. Trial registration The study was retrospectively registered on the ISRCTN registry on 25 November 2012 (ISRCTN88354940).

Introduction: Bronchiectasis (B), commonly seen in patients with chronic obstructive pulmonary disease (COPD), is associated with exacerbations and predicts mortality. Objectives: To differentiate patient groups with COPD‐(B+) or COPD‐(B−) and their exacerbations by using inflammatory markers. Methods: Consecutive COPD patients were divided into two groups according to findings on high resolution thorax CT (HRCT) images using Smith and modified Reiff scores. Patients were prospectively followed for possible future exacerbations. Serum fibrinogen, C‐reactive protein (CRP), soluble urokinase‐type plasminogen activator receptor (suPAR) and Plasminogen activator inhibitor‐1 (PAI‐1) levels were studied during exacerbation and stable periods. Results: Eighty‐seven patients were included and (85 M, 2 F), mean aged was 68.1 ± 9 (46‐87). HRCT confirmed bronchiectasis in 38 (43.7%) patients, most commonly in tubular form (89.4%) and in lower lobes. COPD‐B(+) group had lower body mass index (P = 0.036), more advanced stage of disease (P = 0.004) and more frequent exacerbation (P = 0.01). The HRCT scores were correlated with exacerbation rate (r = 0.356, P < 0.05). Fibrinogen and CRP values were higher in exacerbation (P = 0.01, P = 0.013, respectively) especially in COPD‐B(+) patients. suPAR and PAI‐1 levels were also higher in COPD‐B(+) patients although it was not statistically significant. Conclusion: Bronchiectasis is common and causes frequent exacerbations in COPD. Identifying of COPD‐B(+) phenotype by HRCT scoring systems has considerable importance for both therapeutic options and clinical outcome of the disease. In addition to fibrinogen and CRP, high serum levels of suPAR and PAI‐1 suggest us their significant roles in increased systemic inflammation associated with coexisting of COPD and bronchiectasis. [ABSTRACT FROM AUTHOR]

Soluble urokinase-type plasminogen activator receptor (suPAR) is a membrane-binding protein that is released into the blood stream by immune activation. Recent reports suggest that circulating suPAR levels are associated with adverse cardiovascular outcomes. Exercise tolerance is an independent predictor of prognosis in patients with heart failure (HF); however, the relationship between serum suPAR level and exercise tolerance is unclear. We prospectively enrolled 94 patients who were hospitalized for worsening of HF. All patients underwent a symptom-limited cardiopulmonary exercise test to evaluate exercise tolerance. The median value of serum suPAR was 4848 pg/ml. During follow up, 44 patients (47%) were admitted for all-cause mortality and re-hospitalization for HF. Median serum suPAR was significantly higher in the patients with cardiac events than in the patients with non-event group. Patients were divided into two groups according to circulating suPAR levels. Kaplan–Meier analysis demonstrated that adverse cardiac events were significantly higher in the high suPAR group (log-rank p = 0.023). Multivariate analysis revealed that suPAR was independently correlated with the parameters of exercise tolerance such as anaerobic threshold (p = 0.007) and peak oxygen uptake (p = 0.005). suPAR levels predicted adverse cardiac events and independently correlated with the parameters of exercise tolerance. suPAR could be a useful surrogate biomarker of exercise tolerance in patients with HF. [ABSTRACT FROM AUTHOR]

Introduction: Differentiation between sepsis and systemic inflammation response syndrome (SIRS) remains a diagnostic challenge for clinicians as both may have similar clinical presentation. A quick and accurate diagnostic tool that can discriminate between these two conditions would aid in appropriate therapeutic decision-making. This prospective study was conducted to evaluate the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) and procalcitonin (PCT) in sepsis and SIRS patients. Materials and methods: Eighty-eight patients were enrolled, of which 29 were SIRS and 59 were sepsis patients. The levels of suPAR and PCT were measured on the day of admission (day 1), day 3, and day 7. Results: The levels of suPAR and PCT were significantly higher (p = 0.05 and p < 0.001, respectively) in sepsis group as compared to the SIRS group. The soluble urokinase-type plasminogen activator receptor was a better diagnostic tool in predicting sepsis over PCT [area under curve (AUC) 0.89 vs 0.82] on day 1. The best cutoff for suPAR was 5.58 pg/mL [96% sensitivity and 90% negative predictive value (NPV)] and the best cut-off for PCT was 1.96 ng/mL (93.1% sensitivity and 80% NPV). However, PCT had better prognostic trends (p = 0.006) to identify nonsurvivors in sepsis group. Conclusion: Our findings suggest that both suPAR and PCT can be used as potential test tools to differentiate between SIRS and sepsis. Procalcitonin showed significant prognostic trends to identify nonsurvivors. The soluble urokinase-type plasminogen activator receptor showed better diagnostic potential than PCT on day 1. Clinical significance: Both suPAR and PCT can be used as surrogate biomarkers to distinguish sepsis from SIRS. Procalcitonin showing a significant prognostic trend to identify nonsurvivors can help the clinicians to take relevant clinical decisions. Also, the use of biomarkers like PCT and suPAR could reduce the inappropriate use of antibiotics in noninfective SIRS. [ABSTRACT FROM AUTHOR]

Background: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. Methods: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. Results: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (

Objectives: Sepsis-induced acute kidney injury is the dominant acute kidney injury etiology in critically ill patients and is often associated with a need for renal replacement therapy. The indication and timing of renal replacement therapy are controversially discussed. We hypothesized that the product of the G1-cell cycle arrest biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), and the soluble urokinase-type plasminogen activator receptor are of diagnostic value for the prediction of septic acute kidney injury courses requiring renal replacement therapy.Design: In this prospective study, critically ill patients were enrolled immediately after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2] × [IGFBP7] levels over time and serum soluble urokinase-type plasminogen activator receptor levels once at inclusion were measured. The primary endpoint was the development of septic acute kidney injury with the need for renal replacement therapy. Area under the receiver operating characteristic curves, de Long's tests, and logistic regression models were calculated.Setting: Two ICUs at Heidelberg University Hospital between May 2017 and July 2018.Patients: One-hundred critically ill patients with positive Sepsis-3 criteria.Interventions: None.Measurement and Main Results: Nineteen patients required renal replacement therapy. Diagnostic performance of urinary [TIMP-2] × [IGFBP7] improved over time with the highest area under the receiver operating characteristic curve of 0.89 (95% CI, 0.80-0.98) 24 hours after study inclusion. Soluble urokinase-type plasminogen activator receptor levels at inclusion showed an area under the receiver operating characteristic curve of 0.83 (0.75-0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2] × [IGFBP7] at 24 hours after inclusion by applying a cutoff value of greater than or equal to 0.6 (ng/mL)/1,000 (sensitivity 90.9, specificity 67.1). Soluble urokinase-type plasminogen activator receptor performed best by using a cutoff value of greater than or equal to 8.53 ng/mL (sensitivity 84.2, specificity 82.7). A combination of newly tested biomarkers with cystatin C resulted in a significantly improved diagnostic accuracy. Cystatin C in combination with [TIMP-2] × [IGFBP7] 24 hours outperformed all standard renal parameters (area under the receiver operating characteristic curve 0.93 [0.86-1.00]).Conclusions: [TIMP-2] × [IGFBP7] and soluble urokinase-type plasminogen activator receptor are promising biomarker candidates for the risk stratification of septic acute kidney injury patients with the need for renal replacement therapy. [ABSTRACT FROM AUTHOR]

Urokinase-type plasminogen activator receptor (uPAR) and its soluble form (suPAR) are new injury biomarkers that have been recently suggested to play a vital role in renal diseases. We evaluated the expression of uPAR and the serum concentration of suPAR in type 2 diabetes (T 2 DM) patients with diabetic kidney disease (DKD) to determine the role of this molecule as a biomarker in DKD. The uPAR immunohistochemical staining was performed in biopsy-confirmed DKD renal tissues. Meanwhile, the serum suPAR, Interleukin-18 (IL-18) and C-reactive protein (CRP) levels of 70 diabetic patients with or without DKD and 15 healthy controls were measured. The uPAR expression in DKD patients was significantly increased compared to that in healthy controls and was widely colocalized with the podocyte marker WT1. Meanwhile, serum suPAR and IL-18 levels gradually increased as DKD progressed to the advanced stage. Moreover, serum suPAR and IL-18 levels were negatively correlated with eGFR (ρ = ‒0.734, ρ = ‒0.462, p <0.01) and positively correlated with the urine protein to creatinine ratio (UP/CR) (ρ = 0.730, ρ = 0.440, p <0.01). The suPAR AUC performed better than the IL-18 AUC for the diagnosis of proteinuria (0.845 vs. 0.753, p <0.01) and the decline of renal function (0.895 vs. 0.796, p <0.01). The uPAR expressed in the renal tissues of DKD patients. The soluble form of uPAR, suPAR, can be detected in the serum of DKD patients and has a better diagnostic efficiency in the diagnosis of proteinuria and renal dysfunction in patients with T 2 DM than that of IL-18. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disease resulting in end-stage renal disease in the USA and is increasing in prevalence worldwide. It is a diverse clinical entity with idiopathic, genetic, metabolic, infectious, and other causes that culminate in a characteristic histologic pattern of injury. Proteinuria is a hallmark of FSGS as well as other primary and secondary glomerular disorders. The magnitude of proteinuria at disease onset and during treatment has prognostic implications for renal survival as well as associated cardiovascular morbidity and mortality. Significant advances over the last two decades have shed light on the molecular architecture of the glomerular filtration barrier. The podocyte is the target cell for injury in FSGS. A growing list of disease-causing gene mutations encoding proteins that regulate podocyte survival and homeostasis has been identified in FSGS patients. Several pathogenic and regulatory pathways have been uncovered that result in proteinuria in rodent models and human FSGS. The recurrence of proteinuria and FSGS after kidney transplantation is supporting evidence for the role of a circulating permeability factor in disease pathogenesis. These advances reviewed herein have significant implications for disease classification and therapeutic drug development for FSGS.

Background The aim was to compare serum soluble urokinase-type plasminogen activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women. Methods Our study population consists of voluntary first trimester-pregnant women who applied to the outpatient clinic of the department of obstetrics and gynecology of Ankara Ataturk Training and Research Hospital. Between February and May 2016, 60 pregnant women were included in our prospective study. Serum suPAR and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women with HG and 31 asymptomatic pregnant women were included in the study. Results Serum suPAR level in the HG group was measured as 0.36 ± 0.56 ng/ml, whereas this level in the healthy pregnant control group was measured as 0.15 ± 0.15 ng/ml ( p < 0.05). The interleukin-6 level in the HG group was 5.69 ± 2.16 pg/ml, whereas in the control group it was measured as 3.88 ± 0.28 pg/ml ( p < 0.05). Conclusion Serum suPAR and IL-6 levels proved to be high in the HG group. It is likely that suPAR could play a role in the etiopathogenesis of hyperemesis gravidarum. [ABSTRACT FROM AUTHOR]

Background: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome that presents with proteinuria, usually in the nephrotic range and evidence of histologic lesions of focal and segmental glomerular sclerosis with diffuse foot-process effacement. Recently, suPAR (soluble urokinase-type plasminogen activator receptor) was proposed as the potential circulating causative factor for primary FSGS. Objectives: We performed a cross-sectional study with the aim to determine whether there is a relationship between suPAR serum levels and primary FSGS. The secondary aim was to associate serum suPAR levels with kidney dysfunction. Patients and Methods: We enrolled a total of 90 patients with both suPAR serum levels and proteinuria. From these, 61 patients performed a renal biopsy. Results: The mean age was 49.8 ± 17.2 years, 37 was females (60.7%) and 54 were Caucasian race (91.5%). FSGS was diagnosed in 30 patients (49%). suPAR levels were positive in 34 patients (55.7%) and negative in 27 (44.3%). Concerning the positive results, 17 patients had the histologic diagnosis of FSGS, which gives the test a sensibility of 28%. Concerning the negative results, 14 patients had a different histologic diagnosis other than FSGS, which gives the test a specificity of 23%. The predicted positive value was 50% and the predicted negative value was 52%. suPAR serum levels were not correlated with 24 hours proteinuria (P = 0.5), but we found a positive correlation with C-reactive protein (P = 0.037) and an inverse correlation with estimated glomerular filtration rate (eGFR) (P < 0.001). Conclusions: We found that a positive suPAR test is not a marker of FSGS, but it can be a marker of podocyte and glomerular lesion, as it is inversely correlated with renal function in a cohort of proteinuric patients. Further studies are needed to further validate suPAR as a specific biomarker of glomerular damage. [ABSTRACT FROM AUTHOR]

Serum levels of the soluble urokinase-type plasminogen activator receptor (suPAR) reflect immune and inflammatory activation, and are shown to be associated with cardiovascular outcomes. We herein investigated the potential association between suPAR and left ventricular diastolic dysfunction among patients with preserved left ventricular ejection fraction (LVEF) and sinus rhythm. Among 291 patients who had sinus rhythm and an LVEF of ≥50% enrolled in the study, 26 (8.9%) were considered to have diastolic dysfunction. Patients with diastolic dysfunction had lower estimated glomerular filtration rate (eGFR), and higher systolic blood pressure (BPs), BNP, C-reactive protein, and suPAR than those without diastolic dysfunction. As compared with the first suPAR quartile, the fourth suPAR quartile was significantly associated with both diastolic dysfunction with an odds ratio of 8.95 [95% confidence interval (CI), 1.04-77.0, P < 0.05] after adjusting for sex, age, BPs log(eGFR), CRP, and diuretic use. On the other hand, receiver-operating characteristic curve (ROC) analysis showed that addition of log(suPAR) to the combination of age, sex, and log(eGFR), CRP, and diuretic use did not significantly improve the prediction of diastolic dysfunction. Among cardiac patients with preserved LVEF, serum suPAR was associated with diastolic dysfunction independent of confounding factors by logistic regression analysis. However, according to the ROC analysis, the utility of suPAR as a biomarker for diastolic dysfunction may be limited from a clinical point of view. [ABSTRACT FROM AUTHOR]

Background Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. Methods We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. Results Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis showed that, as compared with the lowest suPAR quartile, the highest suPAR quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence interval, 1.71–24.5) after adjustment for sex, age, log(eGFR), C-reactive protein, and systolic blood pressure. In multivariate receiver operating characteristic analysis to predict NPAF, the area under the curve (AUC) for the combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction (AUC, 0.812; SE, 0.034, P=0.084). Conclusions Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies. [ABSTRACT FROM AUTHOR]

Object: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. Methods: In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/ she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. results: suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). conclusion: Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH. [ABSTRACT FROM AUTHOR]

Background Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. [ABSTRACT FROM AUTHOR]

Hexavalent chromium [Cr(VI)] compounds, known as "Group I Human Carcinogen" and "Category I Respiratory Sensitizer", posed great challenges to the respiratory system. A cross–sectional study was undertaken among chromate workers. Serum club cell protein 16 (CC16) and soluble urokinase–type plasminogen activator receptor (suPAR) were measured using ELISA. Thirteen macrophage–related mediators were tested using cytometric bead array. After controlling for sex, age, smoking status, drinking status and BMI, each increase of one–unit of Ln–transformed blood Cr was related to the increase of IL–1beta [Beta (95% CI), 7.22(1.14, 13.29)%, P = 0.021], IL–23 [8.5(1.15, 15.85)%, P = 0.021], IFN–gamma [3.14(0.15, 6.13)%, P = 0.040], and suPAR [9.31(2.5, 16.12) %, P = 0.008], as well as the increase of CC16 by 3.88(0.42, 7.34) % (P = 0.029). Moreover, these inflammatory mediators played an mediation role in the rise of CC16 caused by Cr(VI). The exposure–response curve analysis revealed a substantial nonlinear association of IFN–gamma and suPAR with CC16, thus the mediation effect of INF–gamma and suPAR required cautious interpretation. The positive connection between macrophage–related mediators was stronger in the high exposure group than in the low exposure group, suggesting that high concentration of chromate might promote a complex interplay within the immune system. [Display omitted] • A cross–sectional study was undertaken among chromate workers. • Blood chromium was positively correlated with serum IL–1beta, IL–23, and IFN–gamma. • Blood chromium was positively correlated with serum suPAR. • IL–1beta, IL–23, IFN–gamma, and suPAR mediated lung injury induced by chromate. • Chromate exposure promoted a complex interplay within the immune system. [ABSTRACT FROM AUTHOR]