Dataset Information

Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis.

ABSTRACT: Introduction:The 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. Methods:Electronic 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. Results:A 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. Conclusions:Our 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.

SUBMITTER: Lee JM

PROVIDER: S-EPMC6476117 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis.

Lee Jiwon M JM Yang Jae Won JW Kronbichler Andreas A Eisenhut Michael M Kim Gaeun G Lee Keum Hwa KH Shin Jae Il JI

Journal of immunology research 20190404

<h4>Introduction</h4>The 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.<h4>Methods</h4>Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earl ...[more]

PMID: 31089477

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Project description:Soluble 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.The 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.suPAR 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).suPAR 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.

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.

Project description:Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade inflammation that plays a major role in immunosenescence and in development and progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, and SCI is typically measured by combining biomarkers of acute inflammation and infection, e.g., CRP, IL-6, and TNFα. In this review, we highlight 10 properties and characteristics that are shared by the blood protein soluble urokinase plasminogen activator receptor (suPAR) and SCI, supporting the argument that suPAR is a biomarker of SCI: (1) Expression and release of suPAR is upregulated by immune activation; (2) uPAR and suPAR exert pro-inflammatory functions; (3) suPAR is associated with the amount of circulating immune cells; (4) Blood suPAR levels correlate with the levels of established inflammatory biomarkers; (5) suPAR is minimally affected by acute changes and short-term influences, in contrast to many currently used markers of systemic inflammation; (6) Like SCI, suPAR is non-specifically associated with multiple diseases; (7) suPAR and SCI both predict morbidity and mortality; (8) suPAR and SCI share the same risk factors; (9) suPAR is associated with risk factors and outcomes of inflammation above and beyond other inflammatory biomarkers; (10) The suPAR level can be reduced by anti-inflammatory interventions and treatment of disease. Assessing SCI has the potential to inform risk for morbidity and mortality. Blood suPAR is a newer biomarker which may, in fact, be a biomarker of SCI since it is stably associated with inflammation and immune activation; shares the same risk factors as many age-related diseases; is both elevated by and predicts age-related diseases. There is strong evidence that suPAR is a prognostic marker of adverse events, morbidity, and mortality. It is associated with immune activity and prognosis across diverse conditions, including kidney disease, cardiovascular disease, cancer, diabetes, and inflammatory disorders. Thus, we think it likely represents a common underlying disease-process shared by many diseases; that is, SCI. We review the supporting literature and propose a research agenda that can help test the hypothesis that suPAR indexes SCI, with the potential of becoming the new gold standard for measuring SCI.

Project description:ObjectiveUsing biomarkers for early and accurate identification of patients at low risk of serious illness may improve the flow in the emergency department (ED) by classifying these patients as nonurgent or even suitable for discharge. A potential biomarker for this purpose is soluble urokinase plasminogen activator receptor (suPAR). We hypothesized that availability of suPAR might lead to a higher proportion of early discharges.DesignA substudy of the interventional TRIAGE III trial, comparing patients with a valid suPAR measurement at admission to those without. The primary endpoint was the proportion of patients discharged alive from the ED within 24 hours. Secondary outcomes were length of hospital stay, readmissions, and mortality within 30 days.SettingEDs at two university hospitals in the Capital Region of Denmark.Participants16,801 acutely admitted patients were included.Measurements and main resultsThe suPAR level was available in 7,905 patients (suPAR group), but not in 8,896 (control group). The proportion of patients who were discharged within 24 hours of admittance was significantly higher in the suPAR group compared to the control group (50.2% (3,966 patients) vs. 48.6% (4,317 patients), P = 0.04). Furthermore, the mean length of hospital stay in the suPAR group was significantly shorter compared to that in the control group (4.3 days (SD 7.4) vs. 4.6 days (SD 9.4), P = 0.04). In contrast, the readmission rate within 30 days was significantly higher in the suPAR group (10.6% (839 patients) vs. 8.8% (785 patients), P < 0.001). Among patients discharged within 24 hours, there was no significant difference in the readmission rate or mortality within 30 days. Readmission occurred in 8.5% (336 patients) vs. 7.7% (331 patients) (P = 0.18) and mortality in 1.3% (52 patients) vs. 1.8% (77 patients) (P = 0.08) for the suPAR group and control group, respectively.ConclusionThese post hoc analyses demonstrate that the availability of the prognostic biomarker suPAR was associated with a higher proportion of discharge within 24 hours and reduced length of stay, but more readmissions. In patients discharged within 24 hours, there was no difference in readmission or mortality.Trial registration of the main trialThis trial is registered with NCT02643459.

Dataset Information

Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis.

Publications

Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis.

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