Plasma suPAR Levels Research Articles

Effect of simvastatin and ezetimibe on suPAR levels and outcomes

Background and aimsSoluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. MethodsWe investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE). ResultsAfter 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%–11.5%) in the placebo group, but only by 4.1% (1.9%–6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17–3.61); MCE 1.40 (1.01–1.92); and AVE 1.42 (1.02–1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE. ConclusionsSimvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

Prospective use of soluble urokinase plasminogen activator receptor to screen TB co-infected with HIV patient among TB patient

BackgroundTuberculosis patient who co infected with the human immunodeficiency virus (HIV) belong to the patient group at high risk for multi-drug resistant TB (TB-MDR). Early recognition is very important to reduce the number of TB/HIV co-infection cases. Soluble urokinase plasminogen activator receptor (suPAR) is considered to be a strong biomarker in HIV as well as TB patients. AimThis study was carried out to evaluate whether suPAR could be used as a biomarker to identify the TB/HIV patients among pulmonary TB-patient. Patients and methodsWe used a cross-sectional study design, in which registered patients were grouped into 3 categories: TB/HIV (n = 15), pulmonary TB-AFB(+) (n = 15), and healthy controls (n = 10). Plasma suPAR levels were measured using ELISA kit. A sputum culture and drug susceptibility test were performed for each patient. ResultssuPAR levels in the TB/HIV group (15.26 ng/mL) were significantly higher (p < 0.05) than those in the TB-AFB (+) group (7.75 ng/mL) and the healthy control group (1.76 ng/mL). ConclusionPlasma suPAR level of TB patients co-infected with HIV showed significantly difference from that of TB-AFB(+) patients suggested its potential to screen the TB/HIV among pulmonary TB-AFB(+) patients.

OP.1A.02] INNATE IMMUNITY AND CARDIO-RENAL RISK IN STAGE 2-5 CKD PATIENTS

Objective: The soluble form of urokinase-type plasminogen activator (suPAR) is a powerful marker for immune activation that accurately predict clinical outcomes in patients with sepsis or infectious diseases. Alterations in innate immunity and Inflammation are major risk factors for the high risk for cardiovascular disease in patients with chronic kidney disease (CKD) but whether suPAR predicts cardiovascular and renal complications independently of established risk factors in CKD is still unknown. Design and method: We measured plasma suPAR levels (ELISA) and a series of traditional and CKD-specific risk factors in 753 stage G2-5 CKD patients. We estimated the risk for GFR loss (>30%) or kidney failure, time to death and first cardiovascular event by multivariate Cox regression analysis adjusting for traditional risk factors and a large series of CKD-specific risk factors. Results: suPAR was gender-dependent and associated with lower GFR and higher proteinuria, older age, diabetes, higher systolic BP, C Reactive Protein (CRP), phosphate, PTH, FGF23, ADMA and lower Hb, 25OH vitD and 1,25OH2 vitD (all P < 0.001). Over a 31 +/− 10 months follow-up 42 patients died and 95 had a renal event. suPAR was a strong predictor of the combined end-point death and cardiovascular events [HR (500pg/ml): 1.09, 95%CI: 1.04–1.14] in a Cox's regression analysis adjusting for a large series of potential confounders including background cardiovascular disease, the GFR, proteinuria, age, gender, smoking, diabetes, systolic BP and anti-hypertensive treatment, phosphate, Hb, serum albumin, BMI, CRP, ADMA and FGF23. Separate analyses of time to death and time to first CV event were both highly significant (P < 0.01) in crude and adjusted analyses. Conclusions: Elevated suPAR levels robustly predict incident cardiovascular events and death in CKD patients. These findings go along with biological knowledge documenting a strong role of suPAR in atherosclerosis and support the contention that suPAR is causally implicated in cardiovascular disease in CKD patients.

A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease.

Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels. Mechanistically, surface plasmon resonance studies identified high-affinity interactions between suPAR, APOL1 and αvβ3 integrin, whereby APOL1 protein variants G1 and G2 exhibited higher affinity for suPAR-activated avb3 integrin than APOL1 G0. APOL1 G1 or G2 augments αvβ3 integrin activation and causes proteinuria in mice in a suPAR-dependent manner. The synergy of circulating factor suPAR and APOL1 G1 or G2 on αvβ3 integrin activation is a mechanism for CKD.

Soluble urokinase-type plasminogen activator receptor and urokinase-type plasminogen activator receptor contribute to chemoresistance in leukemia.

The soluble urokinase-type plasminogen activator receptor (suPAR) and the urokinase-type plasminogen activator receptor (uPAR) have been proposed as useful biomarkers of tumor progression. Recently, suPAR was associated with chemoresistance in lung cancer. However, its clinical significance in leukemia has not previously been investigated. The present study examined the plasma levels of suPAR and the expression of the uPAR on bone marrow (BM) cells in 86 patients with leukemia at diagnosis prior to chemotherapy and 26 normal subjects (control group). The plasma suPAR levels were measured using ELISA, whilst uPAR expression was assayed by flow cytometry analysis. In addition, cell surface uPAR expression on K562 and multidrug-resistant K562/ADM cell lines was studied by western blotting. On admission and follow-up, the levels of suPAR in patients with leukemia were significantly increased compared with controls. Systemic levels of suPAR were strongly associated with the numbers of white blood cells. A case was defined as uPAR-positive (uPAR+) if >20% of the gated cells expressed uPAR. In comparison with 26 healthy BM samples that were negative for uPAR expression, 48 (55.8%) of the 86 leukemia patients were uPAR+. uPAR expression on the cell surface of multidrug-resistant K562/ADM cells was increased compared with that on K562 cells. In conclusion, plasma suPAR expression may be a useful marker for subtype classification of patients with leukemia and cell surface uPAR may be associated with resistance to chemotherapy or disease progression.

Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Is Not Associated with Neurological Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

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. 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. 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). 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.

Soluble CD87 (s-uPAR) predicts bevacizumab-based first line treatment of metastatic colorectal cancer (mCRC): Results from a prospective multi-center study.

604 Background: Bevacizumab-combined chemotherapy is well established in the induction treatment of metastatic colorectal cancer (mCRC). Despite tremendous efforts, no valid predictive marker for anti-VEGF treatment has so far been defined. CD87, the urokinase plasminogen activator receptor (uPAR), is centrally regulating VEGF-induced angiogenesis via adapting endothelial cell migration and invasion (Unseld et al.; ThrombHaem,2015, Brunner et al.; Blood 2011, Prager et al; Blood 2009; Prager et al; Blood 2004). Preoperative plasma s-uPAR levels were shown to independently predicted survival of patients resectable colorectal cancer. This study aimed to identify any prognostic or predictive value of s-uPAR in front-line bevacizumab-treated mCRC patients. Methods: In this prospective multi-center trial (NCT02119026), patients were either treated with bevacizumab plus FOLFOX or bevacizumab plus FOLFIRI. Baseline s-uPAR levels were assessed in 80 patients (40 ea. group) using respective CE-certified electro-chemiluminescence immunoassay (ECLIA). Biomarkers were explored using Kaplan-Meier curves and were log transformed for survival analysis by Cox proportional hazards models. All P values reported are two-sided. Results: Data from eighty patients were available for analysis. Progression free survival (PFS) and overall survival (OS) were assessed. Data indicate significance for the angiogenic biomarker uPAR to determine prognostic (HR = 3.06, CI 1.45 - 6.53, p = 0.003) and predictive (HR = 3.41, CI 2.03 - 5.74, p &lt; 0.001) value in the treatment of Bevacizumab. Conclusions: This is the first prospective analysis of baseline s-uPAR. High baseline-s-uPAR levels were an independent predictive marker for worse bevacizumab-based first-line treatment response.

Plasma Level of Soluble Urokinase-type Plasminogen Activator Receptor Predicts the Severity of Acute Alcohol Pancreatitis.

Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in various inflammatory and infectious diseases. We investigated the activation and prognostic value of plasma suPAR (P-suPAR) in patients experiencing their first acute alcohol pancreatitis (AAP). From prospectively collected data, we measured P-suPAR concentrations in 104 patients with AAP during hospitalization and again after discharge. According to the revised Atlanta classification, pancreatitis was moderately severe in 29 (28%) and severe in 6 (6%) patients and these severities were combined for further analysis (non-mild AAP, n = 35; 34%). Median P-suPAR levels were significantly higher in patients with AAP during hospitalization than after discharge (4.8 vs 3.1 ng/mL; P < 0.001) and in non-mild compared to mild AAP (6.2 vs 4.2 ng/mL; P < 0.001). When the analysis was made 1 to 4 days after admission (n = 68), the area under the curve was 0.81 (95% confidence interval, 0.70-0.92). P-suPAR was found to be a better prognostic marker in AAP than C-reactive protein, hematocrit, or creatinine. P-suPAR concentrations are elevated in AAP and correlate with the severity of the disease. These results suggest that P-suPAR may have potential to serve as a novel prognostic marker for AAP severity on admission.

Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and Impaired Kidney Function in the Population-based Malmö Diet and Cancer Study

IntroductionThe soluble urokinase-type plasminogen activator receptor (suPAR) has recently been associated with a decline in kidney function and incidence of chronic kidney disease in patients with cardiovascular disease undergoing cardiac catheterization, yet little is known whether suPAR is associated with deterioration of kidney function in the general population.MethodsIn the population-based Malmö Diet and Cancer Study cohort, plasma levels of suPAR were quantified in 5381 participants at baseline (1991–1994), and creatinine was measured and used to calculate estimated glomerulus filtration rate (eGFR) at baseline and follow-up (2007–2012). Incident chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 at follow-up.ResultsParticipants within the highest quartile of suPAR had a significantly lower mean eGFR at follow-up than those within the lowest quartile (mean 68 vs. 74 ml/min per 1.73 m2; P-trend = 4.3 × 10–7). In multivariate regression analysis, suPAR (per 1 SD increment of log-transformed suPAR) was associated with a decline in eGFR (P = 3.3 × 10–9) and incident chronic kidney disease (561 events, odds ratio = 1.25; 95% confidence interval, 1.10–1.41). Furthermore, we identified 110 cases of hospitalization due to impaired kidney function via linkage to national registers of inpatient and outpatient hospital diagnoses. During a mean follow-up time of 19 years, suPAR was associated with risk for hospitalization due to impaired kidney function (hazard ratio = 1.49; 95% confidence interval, 1.27–1.74) in multivariate Cox proportional hazard analysis.DiscussionThe increased suPAR level at baseline was associated with a significantly higher longitudinal decline in eGFR, higher incidence of chronic kidney disease, and hospitalization due to impaired kidney function in a cohort of healthy middle-aged participants.

Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels. The placebo period was considered reference and all treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (−1.3 ng/mL), while aliskiren did not. In patients with type 2 diabetes urinary levels of suPAR were reduced during RAS blockade treatment, which may contribute to renoprotection.

Plasma‐soluble urokinase plasminogen activator receptor (suPAR) levels in Behçet's disease and correlation with disease activity

Soluble urokinase plasminogen activator receptor (suPAR), a new biomarker, is a soluble form of membrane-bound receptors secreted from different immune cells. The aim of the present study is to determine plasma suPAR levels in Behçet's disease and their correlation with disease activity. Thirty Behçet's disease patients determined according to the International Study Group criteria for Behçet's disease diagnosis and 41 healthy subjects were included in the present study. Micro-enzyme-linked immunosorbent assay was employed to obtain quantitative data. Data of both groups were statistically analyzed. The comparison of C-reactive protein and suPAR plasma levels of the control and Behçet's disease group revealed statistically significant differences (respectively, P = 0.003 < 0.05 and P = 0.020 < 0.05). However, plasma suPAR levels related with disease activity revealed no statistically significant differences (P > 0.05). The present study is the first study analyzing suPAR levels in Behçet's disease patients and their correlation with disease activity. However, further prospective studies with larger patient series using suPAR as a new plasma biomarker are required to diagnose and monitor Behcet's disease and to support the findings of the present study.

SuPAR level is associated with myocardial impairment assessed with advanced echocardiography in patients with type 1 diabetes with normal ejection fraction and without known heart disease or end-stage renal disease

Heart disease is a common fatal diabetes-related complication. Early detection of patients at particular risk of heart disease is of prime importance. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker for development of cardiovascular disease. We investigate if suPAR is associated with early myocardial impairment assessed with advanced echocardiographic methods. In an observational study on 318 patients with type 1 diabetes without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF >45%), we performed conventional, tissue Doppler and speckle tracking echocardiography, and measured plasma suPAR levels. Associations between myocardial function and suPAR levels were studied in adjusted models including significant covariates. Patients were 55±12 years (mean±s.d.) and 160 (50%) males. Median (interquartile range) suPAR was 3.4 (1.7) ng/mL and LVEF was 58±5%. suPAR levels were not associated with LVEF (P=0.11). In adjusted models, higher suPAR levels were independently associated with both impaired systolic function assessed with global longitudinal strain (GLS) and tissue velocity s', and with impaired diastolic measures a' and e'/a' (all P=0.034). In multivariable analysis including cardiovascular risk factors and both systolic and diastolic measures (GLS and e'/a'), both remained independently associated with suPAR levels (P=0.012). In patients with type 1 diabetes with normal LVEF and without known heart disease, suPAR is associated with early systolic and diastolic myocardial impairment. Our study implies that both suPAR and advanced echocardiography are useful diagnostic tools for identifying patients with diabetes at risk of future clinical heart disease, suited for intensified medical therapy.

Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models.

BackgroundsuPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models.MethodsClinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA−/−) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied.ResultsFSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA−/− group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA−/− group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G.ConclusionsA deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.

Soluble Urokinase Receptor and Chronic Kidney Disease

BackgroundRelatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease.MethodsWe measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables.ResultsA higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile.ConclusionsAn elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.)

Clinical value of soluble urokinase-type plasminogen activator receptor in the diagnosis, prognosis, and therapeutic guidance of sepsis

ObjectivesThe level of soluble urokinase-type plasminogen activator receptor (suPAR) is significantly increased in sepsis. We investigated whether suPAR could be a valuable biomarker in sepsis. MethodsWe measured suPAR and procalcitonin (PCT) levels, recorded the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores of engaged subjects, and drew Receiver Operating Characteristics curves. ResultsThe plasma suPAR and serum PCT levels of the sepsis group were higher than those of the systemic inflammatory response syndrome and control groups. Using suPAR to distinguish systemic inflammatory response syndrome from sepsis on day 1, the area under the curve (AUC) curve was 0.817, and when suPAR and PCT were used in combination to diagnose sepsis, the AUC was 0.927. At a cutoff point of 9.52 ng/mL, the sensitivity and specificity for diagnosis of sepsis using suPAR were 71.93% and 95.46%, respectively. At a cutoff point of 12.01 ng/mL, the sensitivity and specificity for distinguishing survival and mortality by suPAR were 87.1% and 72.5%, respectively. When suPAR and the APACHE II score were combined to distinguish survival from mortality, the AUC was 0.857. The plasma suPAR level was positively correlated with the serum PCT level (r = 0.326, P < .001), APACHE II score (r = 0.492, P < .001), and Sequential Organ Failure Assessment score (r = 0.386, P < .001). ConclusionsUse of both plasma suPAR and PCT levels enhanced the efficiency of sepsis diagnosis, and the combination of plasma suPAR and APACHE II score improved mortality prediction.

Increased Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in Plasma of Suicide Attempters.

The soluble form of the urokinase receptor, suPAR, has been suggested as a novel biomarker of low-grade inflammation. Activation of the immune system has been proposed to contribute to the development of depression and suicidal behavior. In order to identify depressed and suicidal individuals who could benefit from an anti-inflammatory treatment, a reliable biomarker of low-grade inflammation is vital. This study evaluates plasma suPAR levels as a biomarker of low-grade inflammation in patients with major depressive disorder and in patients who recently attempted suicide. The plasma suPAR and an established biomarker, C reactive protein (CRP) of suicide attempters (n = 54), depressed patients (n = 19) and healthy controls (n = 19) was analyzed with enzyme-linked immunosorbent assays. The biomarker attributes of sensitivity and sensibility were evaluated using ROC curve analysis. Both the depressed patients and suicide attempters had increased plasma suPAR. The levels of suPAR discriminated better between controls and suicide attempters than did CRP. In the future, plasma suPAR might be a superior prognosticator regarding outcome of treatment applying conventional antidepressants in conjunction with anti-inflammatory drugs.

Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China.

BackgroundSoluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN).MethodsWe measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed.ResultsWe found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions.ConclusionsOur study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN.

Plasma Soluble Urokinase Receptor Level Is Correlated with Podocytes Damage in Patients with IgA Nephropathy.

BackgroundFocal segmental glomerulosclerosis (FSGS) lesions are similar in characteristics to S lesions of the Oxford classification of IgA nephropathy (IgAN) and may predict poor prognosis. In the present study, we aimed to explore the association between plasma soluble urokinase receptor (suPAR) levels and S lesions and podocytes damage in IgAN patients.MethodsWe enrolled 569 IgAN patients with follow-up data and detected plasma suPAR levels at renal biopsy by enzyme-linked immunosorbent assay.ResultsPlasma suPAR levels in IgAN patients with or without S lesions did not differ significantly (P = 0.411). However, suPAR levels were positively correlated with proteinuria (r = 0.202, P < 0.001), and negatively correlated with estimated glomerular filtration rate (eGFR, r = –0.236, P < 0.001). In the partial correlation to adjust for eGFR, plasma suPAR levels remained positively correlated with proteinuria (r = 0.112, P = 0.023). In a Cox proportional hazards model, higher levels of plasma suPAR were not associated with poor renal outcome. Plasma suPAR levels of IgAN and primary FSGS patients with nephrotic syndrome were not significantly different (P = 0.306). Plasma suPAR levels in patients with extensive effacement of the epithelial cell foot processes of glomerular podocytes were significantly higher than those with segmental effacement on the basis of comparable eGFR (P = 0.036).ConclusionsIn IgAN patients, plasma suPAR levels were not associated with S lesions. However, they were positively associated with proteinuria and negatively associated with eGFR. In addition, plasma suPAR levels were positively associated with the effacement degree of the foot processes, which might partially contribute to the development of proteinuria in patients with IgAN.

The value of soluble urokinase plasminogen activator receptor in diagnosis and severity assessment of sepsis

Objective To determine the diagnostic and assessment value of soluble urokinase plasminogen activator receptor (suPAR) level in septic patients. Methods Totally 82 septic patients in the Department of Intensive Care Unit of The First Affiliated Hospital, Sun Yat-Sen University were prospectively analyzed from June 2013 to March 2014. Another 29 patients with systemic inflammatory response syndrome (SIRS) and 15 healthy subjects served as controls. Septic patients were divided into sepsis group (n=27) , severe sepsis group (n=27) and septic shock group (n=28) according to the severity, and there was no significant difference in age and sex among these groups. Measurement of plasma suPAR, serum procalcitonin (PCT) and C-reactive protein (CRP) levels, and calculation of acute physiology and chronic health evaluationⅡ (APACHEⅡ) and sequential organ failure assessment (SOFA) score were performed. Comparison of group differences for continuous variables was done by one-way ANOVA or nonparametric Kruskal-Wallis test. Spearman rank correlation analysis was applied to establish the relation between variables. Receiver operating characteristics (ROC) curve was created and area under curve (AUC) was calculated to determine the diagnostic value of these variables in sepsis. Results The levels of plasma suPAR in SIRS group, sepsis group, severe sepsis group, septic shock group, and healthy control group were (8.22±0.61) , (11.45±1.12) , (12.99±1.28) , (15.75±1.23) and (4.65±0.30) ng/ mL, respectively. Plasma suPAR levels in SIRS group and sepsis group were higher than that in healthy control group (P<0.01) , and elevated plasma suPAR was accompanied by increased severity of sepsis (P<0.05). PCT levels of sepsis group (17.66±8.42) ng/ mL, severe sepsis group (9.67±3.56) ng/mL and septic shock group (29.19±10.78) ng/ mL were greater than that in SIRS group (1.10±0.78) ng/ mL, P<0.01. CRP levels elevated in all groups, but there were no significant differences among them. When suPAR and CRP were applied to distinguishing sepsis from SIRS, the AUC values from suPAR and combination of suPAR and PCT were 0.817 (P <0.01, 95%CI: 0.714-0.921) and 0.927(P<0.01, 95%CI: 0.870–0.985), respectively. Using 9.52 ng/ mL suPAR as the best cut-off to distinguish sepsis from SIRS, there were 71.93% sensitivity and 95.46% specificity. The levels of plasma suPAR positively correlated with PCT levels (r=0.326) , APACHE Ⅱ score (r=0.492) and SOFA score (r=0.386) , P<0.01. Conclusions Plasma suPAR levels significantly elevated in septic patients and correlated with the severity of sepsis. Sepsis and SIRS may be discerned by plasma suPAR levels. Joint use of suPAR and PCT could greatly increase the specificity of diagnosis of sepsis. Key words: Sepsis; suPAR; PCT; CRP; Diagnosis

Assessment of Soluble Urokinase-Type Plasminogen Activator Receptor (supAR) in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a disease characterized by a progressive airflow limitation. Soluble urokinase-type plasminogen activator receptor (suPAR) is released from the membrane-bound plasminogen activator, and is positively correlated with the activation of immune system.Aims: Release of inflammatory mediators is increased in chronic obstructive pulmonary disease (COPD), particularly during exacerbations. The objective of this study was to compare plasma levels of suPAR and serum levels of C-reactive protein (CRP) during exacerbation and stable periods in patients with COPD.Study Design: Prospective clinical study. Methods: The patients with COPD were divided into 3 groups for evaluations: those with stable COPD [SCOPD] (n= 54), pre-treatment acute exacerbation COPD [AECOPD] (n= 53), and post-treatment AECOPD (n= 52). Plasma suPARand serum CRP levels were assessed for each patient.Results: Whereas the increased serum CRP levels of the participants were 54.82±56.63 mg/l during acute exacerbation period, during the stable period it was 5.02±6.31 mg/l and statistically significant (p= 0.0001). The suPAR level was 1.28±0.52ng/ml during the acute exacerbation period vs.1.21±0.59ng/ml during the stable period, without a difference (p= 0.49). There was a statistically significant decrease in the CRP serum levels; yet, although not statistically significant  a remarkable decrease was seen in the suPAR levels obtained before and after the management of exacerbations (p= 0.001 and p= 0.06 respectively).Conclusion: These results support the idea that suPAR, a novel biomarker, might be an important indicator if verified with further prospective studies in evaluating COPD exacerbations and treatment response like CRP used for decades.