Soluble urokinase-type plasminogen activator receptor in FSGS: stirred but not shaken.
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ABSTRACT:
SUBMITTER: Reiser J
PROVIDER: S-EPMC4116074 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
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Soluble urokinase-type plasminogen activator receptor in FSGS: stirred but not shaken.
Reiser Jochen J Chapman Harold H
Journal of the American Society of Nephrology : JASN 20140501 8
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Project description:IntroductionThe soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS.MethodsElectronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale.ResultsA total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants = 814; studies = 9, I 2 = 85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference.ConclusionsOur meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.
| S-EPMC6476117 | biostudies-literature
Project description:Background and objectivesSoluble urokinase plasminogen activator receptor (suPAR) was initially proposed as a pathogenic and predictive biomarker of primary FSGS, but the findings were controversial. This study aimed to clarify the clinical implications of suPAR.Design, setting, participants, & measurementsThe study enrolled 109 patients with biopsy-proven primary FSGS who were administered prednisone between January 2011 and May 2013 and followed up for 6-24 months (median duration of follow-up, 12 months). Ninety-six healthy volunteers, 20 patients with minimal-change disease (MCD), and 22 patients with membranous nephropathy (MN) served as controls. Serum suPAR levels were measured using ELISA.ResultssuPAR levels in patients with FSGS (median, 3512 [interquartile range (IQR), 2232-4231] pg/ml) were significantly higher than in healthy controls (median, 1823 [IQR, 1563-2212] pg/ml; P<0.001), patients with MCD (median, 1678 [IQR, 1476-2182] pg/ml; P<0.001), and patients with MN (median, 1668 [IQR, 1327-2127] pg/ml; P<0.001). With 3000 pg/ml used as a threshold, suPAR levels were elevated in 48.6% of patients with FSGS, in contrast to 5% of patients with MCD and 4.5% of those with MN. suPAR levels were independently associated with steroid response in patients with FSGS (odds ratio, 85.02; P=0.001). Patients who were sensitive to steroids had significantly higher suPAR levels than nonsensitive patients (median, 3426 [IQR, 2670-5655] pg/ml versus 2523 [IQR, 1977-3460] pg/ml; P=0.001). A suPAR level of 3400 pg/ml was chosen as the optimal cutoff value for steroid response. At the 6-month follow-up in 84 patients with FSGS, suPAR levels were significantly decreased in those with suPAR level ≥ 3400 pg/ml (median, 4553 [IQR, 3771-6120] pg/ml versus 3149 [IQR, 2278-3953]; P=0.002) but were unchanged in patients with suPAR level <3400 pg/ml (median, 2359 [IQR, 2023-2842] pg/ml versus 2490 [IQR, 1916-3623] pg/ml; P=0.09).ConclusionssuPAR is specifically elevated in some patients with FSGS, which differs from the finding in patients with MCD and MN. A suPAR assay may help predict steroid response in patients with primary FSGS.
| S-EPMC4220753 | biostudies-literature
Project description: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.
| S-EPMC5494859 | biostudies-other
Project description:Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.
| S-EPMC7074407 | biostudies-literature
Project description:Background and objectivesBlack Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.Design, setting, participants, & measurementsUsing data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.ResultsAt baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02).ConclusionsHigher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.
| S-EPMC6032570 | biostudies-literature
Project description:Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with chronic kidney disease (CKD) severity and peripheral artery disease (PAD). We hypothesize an association of PAD severity and suPAR in patients without advanced CKD and further risk stratification according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. For study purposes, suPAR was measured in 334 PAD patients (34% women, age 69 (62-78) years, eGFR 68 ± 20 mL/min/1.72 m2) by commercial ELISA. Patients were followed for 10 years to assess long-term all-cause survival by Cox regression. Higher suPAR levels were associated with lower ankle-brachial index (R = -0.215, p = 0.001) in patients with PAD without media-sclerosis (n = 236). suPAR levels inversely correlated with decreased glomerular filtration rate (R = -0.476, p < 0.001) and directly correlated with urinary albumin-to-creatinine ratio (R = 0.207, p < 0.001). Furthermore, higher suPAR levels associated with a higher KDIGO risk score (p < 0.001). Baseline suPAR was significantly associated with all-cause mortality (HR 1.40 (95% CI 1.16-1.68), p < 0.001) over 10 years. suPAR remained associated with mortality (HR 1.29 (1.03-1.61), p = 0.026) after multivariable adjustment for age, sex, cardiovascular risk factors, and eGFR. Future research may define a standard role for suPAR assessment in PAD's work-up and treatment, especially in patients with CKD.
| S-EPMC7879231 | biostudies-literature
Project description:AimsSoluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS.Methods and resultsSuPAR levels were determined in serial plasma samples (0-96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2-6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0-15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category.ConclusionSuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.
| S-EPMC9629697 | biostudies-literature
Project description:BACKGROUND:The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in severe acute and chronic medical conditions and has been associated with short-term mortality. The role of suPAR in predicting risk of death following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has never been studied. We hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure. METHODS:This retrospective cohort study from a university hospital in the Capital Region of Denmark included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis, who had plasma suPAR measured at the time of admission between November 18th, 2013 to September 30th, 2015 and followed until December 31st, 2015. Primary outcomes were 30- and 90-days all-cause mortality. Association of suPAR and mortality was investigated by Cox regression analyses adjusted for age, sex, CRP values and Charlson comorbidity index. RESULTS:For patients with AECOPD or underlying COPD, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P <?0.0001). Increasing suPAR levels independently predicted 30-day mortality in patients with COPD with a hazard ratio of 2.0 (95% CI 1.7-2.4) but not respiratory failure. CONCLUSIONS:In this large group of acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality. The study supports the value of suPAR as a marker of poor prognosis.
| S-EPMC5963104 | biostudies-literature
Project description: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.
| S-EPMC4599802 | biostudies-literature
Project description:BackgroundThe soluble urokinase plasminogen activator receptor (suPAR) is related to hepatic inflammation and fibrosis and has been suggested to participate in the development of liver cirrhosis. Therefore, the aim of the current study was to measure the concentration of suPAR in the hepatic vein of cirrhotic patients during a liver vein catheterization to identify a possible hepatic suPAR generation. Furthermore, we explored if suPAR levels were associated with the degree of cirrhosis and liver dysfunction.Methods and patientsWe included 105 cirrhotic patients and 19 liver-healthy controls. Blood was sampled from the hepatic vein and the femoral artery and suPAR was measured by enzyme-linked immunosorbent assay.ResultsWe identified significantly higher median suPAR concentrations among the cirrhotic patients (7.2 ng/ml in the hepatic vein; 6.8 ng/ml in the femoral artery) compared to the controls (2.6 ng/ml, respectively, p-values <0.001). However, the median hepatic suPAR formation was 0.0 ng/ml in both groups. We observed significantly increasing suPAR levels according to higher Child classes (4.5 ng/ml, 6.9 ng/ml and 9.0 ng/ml, Child A, B, C respectively; p-value<0.001), and significantly higher median suPAR concentrations in patients with ascites versus patients without ascites (8.1 ng/ml versus 5.3 ng/ml, respectively, p-value<0.001). suPAR levels were significantly related to bilirubin (r = 0.48, p<0.001), the hepatic venous pressure gradient (r = 0.39, p<0.001), the cardiac index (r = 0.24, p = 0.02) and the plasma volume (r = 0.33, p = 0.001), whereas suPAR levels were significantly inversely related to albumin (r = -0.59, p<0.001), plasma coagulation factors (r-0.39, p<0.001), the mean arterial pressure (r = -0.28, p = 0.004), the systemic vascular resistance (r = 0.26, p = 0.007), the indocyanine green clearance (r = -0.51, p<0,001) and the galactose elimination capacity (r = -0.39, p<0.001).ConclusionWe identified elevated suPAR concentration in cirrhotic patients, which correlated significantly with the degree of cirrhosis and liver failure, but we were not able to demonstrate hepatic suPAR generation per se. This suggests that further investigations of the source of suPAR in cirrhotic patients need to be undertaken.
| S-EPMC6715219 | biostudies-literature