Dataset Information

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

ABSTRACT: 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.

SUBMITTER: Bocskei RM

PROVIDER: S-EPMC7074407 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Bocskei Renata Marietta RM Meszaros Martina M Tarnoki Adam Domonkos AD Tarnoki David Laszlo DL Kunos Laszlo L Lazar Zsofia Z Bikov Andras A

Medicina (Kaunas, Lithuania) 20200214 2

<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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. ...[more]

PMID: 32075014

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Project description:BACKGROUND AND OBJECTIVES:Black 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, & MEASUREMENTS:Using 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. RESULTS:At 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). CONCLUSIONS:Higher 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.

Project description:Background & Aims:Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. Methods:Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. Results:High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. Conclusion:Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. Lay summary:Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

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.

Dataset Information

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Publications

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

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