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Keywords = soluble urokinase plasminogen activator receptor

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13 pages, 647 KB  
Article
Increased suPAR Plasma Levels May Indicate Postoperative Sepsis Following Open Thoracoabdominal Aortic Repair
by Dragos Socol, Cathryn Bassett, Bernhard Hruschka, Jelle Frankort, Moustafa Elfeky, Katja Heller, Florian Kahles, Berkan Kurt, Christian Uhl, Panagiotis Doukas and Alexander Gombert
J. Clin. Med. 2025, 14(24), 8843; https://doi.org/10.3390/jcm14248843 - 14 Dec 2025
Viewed by 318
Abstract
Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative [...] Read more.
Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative dynamics of soluble urokinase plasminogen activator receptor (suPAR) plasma levels in TAAA patients undergoing elective surgical repair and evaluates its diagnostic potential for early detection of postoperative sepsis. Methods: In this retrospective, single-center study, 28 patients (mean age 52.6 ± 13.4 years; 67.9% male) underwent elective open TAAA repair between 2022 and 2024. Blood samples were collected at five perioperative time points, and suPAR levels were measured using ELISA. The primary endpoint was the onset of postoperative sepsis, with secondary endpoints including other organ complications. The predictive performance of suPAR levels was evaluated using Receiver Operator Characteristics (ROC) analysis. Results: Postoperative sepsis developed in 7 of 28 patients (25%), with the diagnostic criteria met at a mean of 9.7 ± 6.9 days. Baseline suPAR levels did not differ between groups; however, from 12 h after surgery, the sepsis group exhibited significantly higher serum concentrations (14.43 ng/mL vs. 7.23 ng/mL; p = 0.004), a difference that persisted throughout the first 24 h. At 24 h, suPAR had the highest predictive accuracy for sepsis, with an AUC of 0.90, 90% sensitivity, and 86% specificity at a 9 ng/mL cut-off (p < 0.001). Conclusions: Elevated suPAR levels in the early postoperative period are strongly associated with the later onset of sepsis. Early monitoring may enable timely intervention, potentially improving outcomes in this high-risk patient population. Full article
(This article belongs to the Section Cardiovascular Medicine)
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12 pages, 915 KB  
Article
Soluble Urokinase Plasminogen Activator Receptor (suPAR) Predicts 28-Day and 90-Day Mortality in Emergency Department Patients with Chest Pain, Dyspnoea, or Abdominal Pain
by Francesco Gavelli, Francesca Maria Giolitti, Matteo Vidali, Marta Montersino, Matteo Bertoli, Luca Molinari, Marco Baldrighi, Michela Beltrame, Pier Paolo Sainaghi, Mattia Bellan, Filippo Patrucco, Gian Carlo Avanzi and Luigi Mario Castello
Diagnostics 2025, 15(22), 2851; https://doi.org/10.3390/diagnostics15222851 - 11 Nov 2025
Viewed by 533
Abstract
Background: Early stratification of patients at emergency department (ED) admission is crucial. The soluble urokinase plasminogen activator receptor (suPAR) has emerged as a promising biomarker to identify the worsening of different clinical conditions. We aimed at evaluating whether baseline suPAR values predict 28-day [...] Read more.
Background: Early stratification of patients at emergency department (ED) admission is crucial. The soluble urokinase plasminogen activator receptor (suPAR) has emerged as a promising biomarker to identify the worsening of different clinical conditions. We aimed at evaluating whether baseline suPAR values predict 28-day and 90-day mortality in patients presenting to the ED with different conditions. Methods: In this prospective observational study, we enrolled patients with dyspnoea (D), chest pain (CP), and abdominal pain (AP). suPAR levels, together with clinical and laboratory data, were recorded at ED admission. The data collected included 28-day and 90-day mortality data, as well as 28-day and 90-day hospital readmission; and their correlation with suPAR values was assessed. Results: We enrolled 298 consecutive patients (CP 23.8%, D 31.9%, AP 44.3%). suPAR was significantly higher in patients with dyspnoea, compared to both patients with chest and abdominal pain (5.50 [3.50–8.60], 3.20 [2.30–4.10], 3.20 [2.33–4.48] ng/mL, respectively; p < 0.001). suPAR plasmatic levels were also higher in patients admitted to semi-intensive or intensive care units compared to other patients (4.10 [3.15–8.05] vs. 3.50 [2.55–5.50] ng/mL, respectively; p = 0.049). suPAR levels were significantly higher in patients dead at 28 days than in survivors (12.65 [9.83–18.53] vs. 3.60 [2.60–5.48] ng/mL, respectively; p < 0.001). Using the stepwise logistic regression analysis, only suPAR emerged as an independent predictor of 28-day mortality with an odds ratio of 1.31 (95% CI 1.10–1.56). Conclusions: Baseline suPAR levels are an independent predictor of mortality in ED patients with chest pain, dyspnoea, or abdominal pain. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Management in Emergency and Hospital Medicine)
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22 pages, 346 KB  
Review
Serum Factors in Primary Podocytopathies
by Edward John Filippone and John L. Farber
Antibodies 2025, 14(4), 82; https://doi.org/10.3390/antib14040082 - 28 Sep 2025
Viewed by 1176
Abstract
Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells [...] Read more.
Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include annexin, the proteosome, podocin, and CD40. Additionally, high-resolution confocal microscopy has identified punctate immunoglobulin deposits along the slit diaphragm and podocyte cell body that may or may not colocalize with abnormal punctate nephrin staining and may correlate with detectable circulating antibodies. The success of rituximab in observational studies in both native kidneys and transplants supports a primary role for autoantibodies. We discuss in detail the data supporting putative non-antibody circulating factors, as well as the recent data supporting antibody pathogenesis, which may provide some clues on treating the individual patient. Full article
(This article belongs to the Section Humoral Immunity)
14 pages, 791 KB  
Article
Assessment of Cardiorenal Involvement in Systemic Sclerosis Patients
by Chiara Pellicano, Giancarlo D’Ippolito, Annalisa Villa, Ottavio Martellucci, Umberto Basile, Valeria Carnazzo, Valerio Basile, Edoardo Rosato, Mariapaola Marino and Antonietta Gigante
Biomolecules 2025, 15(9), 1297; https://doi.org/10.3390/biom15091297 - 9 Sep 2025
Viewed by 971
Abstract
Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart [...] Read more.
Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiorenal Syndrome)
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14 pages, 681 KB  
Article
Soluble Urokinase Plasminogen Activator Receptor (suPAR) Plasma Concentration Is Reduced Using Minimized Extracorporeal Circulation: Results of a Secondary Analysis of a Prospective Observational Study
by Thomas S. Zajonz, Fabian Edinger, Juliane Götze, Melanie Markmann, Michael Sander, Christian Koch and Emmanuel Schneck
J. Clin. Med. 2025, 14(14), 5020; https://doi.org/10.3390/jcm14145020 - 16 Jul 2025
Viewed by 1133
Abstract
Background: Minimized extracorporeal circulation (miECC) was developed to mitigate the adverse effects of cardiopulmonary bypass (CPB), yet its impact on soluble urokinase plasminogen activator receptor (suPAR) is unclear. SuPAR has been linked to adverse outcomes, including acute kidney injury (AKI). This study investigated [...] Read more.
Background: Minimized extracorporeal circulation (miECC) was developed to mitigate the adverse effects of cardiopulmonary bypass (CPB), yet its impact on soluble urokinase plasminogen activator receptor (suPAR) is unclear. SuPAR has been linked to adverse outcomes, including acute kidney injury (AKI). This study investigated perioperative suPAR kinetics in patients undergoing cardiac surgery with miECC or conventional CPB (cCPB) and explored its association with AKI, postoperative delirium (POD), and infections. Methods: This study is a secondary analysis of an observational cohort of 79 cardiac surgical patients. It evaluates perioperative suPAR levels and their association with the type of CPB used (miECC vs. cCPB) and postoperative adverse outcomes, including POD, AKI, and infections. Statistical analyses included repeated measures ANOVA, Wilcoxon tests, logistic regression, and ROC curve analysis to assess the predictive value of suPAR for these outcomes. Results: During surgery, suPAR significantly increased to higher levels with the use of cCPB compared to miECC (p = 0.027; odds ratio of 0.69 [0.57–0.84], p < 0.001). The use of miECC was an independent influencing factor on suPAR (−0.41 ± 0.1; p < 0.001). Regardless of the type of CPB, suPAR levels differed significantly between patients with and without kidney damage (n = 25; no AKI: 1.6 [1.1–2.0], AKI: 1.7 [1.3–2.4], p < 0.001). Multivariate regression analysis showed that AKI was an independent influencing factor on suPAR (−0.49 ± 0.1; p < 0.001). SuPAR demonstrated only low predictive value for AKI and could not predict POD. Conclusions: This study provides evidence that miECC is associated with lower intraoperative suPAR levels, suggesting a reduced inflammatory response compared to cCPB. While suPAR levels were significantly higher in patients with AKI, their predictive value for AKI remains limited. Furthermore, suPAR did not predict POD but was elevated in patients with pneumonia. Full article
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19 pages, 395 KB  
Article
Assessment of Serum suPAR Levels in Patients with Group 1 and Group 4 Pulmonary Hypertension
by Abdullah Tunçez, Muhammed Ulvi Yalçın, Hüseyin Tezcan, Bülent Behlül Altunkeser, Bahadır Öztürk, Canan Aydoğan, Aslıhan Toprak, Onur Can Polat, Nazif Aygül, Kenan Demir, Kadri Murat Gürses, Yasin Özen, Fikret Akyürek and Hatice Betül Tunçez
J. Clin. Med. 2025, 14(13), 4671; https://doi.org/10.3390/jcm14134671 - 2 Jul 2025
Viewed by 902
Abstract
Background/Objectives: Pulmonary hypertension (PH) is a progressive disorder with high morbidity and mortality, partly driven by chronic inflammation. Soluble urokinase plasminogen activator receptor (suPAR) reflects immune activation. We evaluated whether suPAR is altered in Group 1 and Group 4 PH and its association [...] Read more.
Background/Objectives: Pulmonary hypertension (PH) is a progressive disorder with high morbidity and mortality, partly driven by chronic inflammation. Soluble urokinase plasminogen activator receptor (suPAR) reflects immune activation. We evaluated whether suPAR is altered in Group 1 and Group 4 PH and its association with clinical, echocardiographic, and laboratory parameters. Methods: We enrolled 44 PH patients (36 in Group 1, 8 in Group 4) and 45 healthy controls. All underwent clinical and echocardiographic assessments; right heart catheterization was performed in the PH patients. Serum suPAR was measured by ELISA. N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were also assessed. Results: The suPAR plasma levels in the PH group were between 23.91 and 960.8 pg/mL (median: 73.14 p25: 62.77, p75: 167.13). suPAR was significantly higher in PH versus controls (73.14 [62.77–167.13] vs. 65.52 [53.06–80.91] pg/mL; p = 0.012). In logistic regression, systolic blood pressure, erythrocyte sedimentation rate, NT-proBNP, and suPAR independently predicted PH. suPAR correlated negatively with six-minute walk distance (r = −0.310) and tricuspid annular plane systolic excursion (r = −0.295) but positively with systolic pulmonary artery pressure (r = 0.241). On multivariate analysis, six-minute walk distance was the only independent correlate of suPAR (p = 0.004). suPAR levels did not differ between Group 1 and Group 4 PH. Conclusions: suPAR is elevated in Group 1 and Group 4 PH and correlates with functional and echocardiographic indices of disease severity. Larger prospective studies are needed to determine suPAR’s role in diagnosis, risk stratification, and therapeutic decision-making. Full article
(This article belongs to the Section Cardiovascular Medicine)
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23 pages, 389 KB  
Review
New and Emerging Biomarkers in Chronic Kidney Disease
by Mikołaj Dopierała, Nadja Nitz, Oliwia Król, Karolina Wasicka-Przewoźna, Krzysztof Schwermer and Krzysztof Pawlaczyk
Biomedicines 2025, 13(6), 1423; https://doi.org/10.3390/biomedicines13061423 - 10 Jun 2025
Cited by 8 | Viewed by 7767
Abstract
Chronic kidney disease (CKD) represents a major and widespread global health challenge. It affects over 800 million people worldwide, which is approximately 13% of the world’s population. Over the past 20 years, it has consistently ranked among the leading causes of death. As [...] Read more.
Chronic kidney disease (CKD) represents a major and widespread global health challenge. It affects over 800 million people worldwide, which is approximately 13% of the world’s population. Over the past 20 years, it has consistently ranked among the leading causes of death. As a result of its typically painless and asymptomatic presentation in the early stages of the disease, CKD is frequently diagnosed late, when the patient is already suffering from serious complications. In recent years, studies have identified novel biomarkers associated with the pathophysiology of CKD, including chronic inflammation, tubular injury, and CKD-related outcomes such as bone and mineral metabolism disorders, cardiovascular events, and all-cause mortality. Identifying and using these emerging biomarkers—like kidney injury molecule, N-acetyl–D-glucosaminidase, ficolins, the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome, soluble suppression of tumorigenicity-2, galectin-3, growth differentiation factor-15, soluble urokinase-type plasminogen activator receptor, sclerostin, the Dick-kopf proteins, and indexes such as the systemic inflammation response index—may lead to a significant advancement in early diagnosis, risk stratification, and personalized treatment strategies for CKD patients. Despite their potential, the routine clinical use of these novel biomarkers remains limited due to challenges such as high costs and the lack of standardized testing methods. There is still considerable room for advancement in both the diagnosis and management of CKD. Hopefully, increasingly more new biomarkers will become usable in clinical practice, ultimately improving care quality and outcomes for patients with CKD. Full article
11 pages, 652 KB  
Article
Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Erectile Dysfunction in Diabetic Patients
by Osman Erinc, Ozgur Yilmaz, Tacettin Yekta Kaya, Murvet Algemi and Murat Akarsu
J. Clin. Med. 2025, 14(12), 4029; https://doi.org/10.3390/jcm14124029 - 6 Jun 2025
Viewed by 1248
Abstract
Background/Objectives: Erectile dysfunction (ED) is a common complication of diabetes mellitus (DM), largely attributable to vascular, neurological and metabolic dysfunctions. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation and endothelial dysfunction, both of which play key roles in ED [...] Read more.
Background/Objectives: Erectile dysfunction (ED) is a common complication of diabetes mellitus (DM), largely attributable to vascular, neurological and metabolic dysfunctions. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation and endothelial dysfunction, both of which play key roles in ED pathophysiology. This study aimed to evaluate the relationship between serum suPAR levels and ED in patients with type 2 DM, assessing its potential as a biomarker for early detection. Methods: This prospective, cross-sectional study included 127 male patients with type 2 DM and 46 healthy controls. Erectile function was assessed using the International Index of Erectile Function-5. Patients were divided into three groups: controls, diabetic patients without ED (DM-NoED) and diabetic patients with ED (DMED). Serum suPAR levels were measured via ELISA. Statistical analyses included Kruskal–Wallis tests, Dunn’s post hoc comparisons and ROC curve analysis to evaluate diagnostic performance. Results: Serum suPAR levels were significantly elevated in the DMED group compared to both the DM-NoED and control groups (p < 0.001). The median suPAR levels were 107.9 pg/mL (controls), 130.3 pg/mL (DM-NoED) and 218.7 pg/mL (DMED). ROC analysis revealed an AUC of 0.836 in distinguishing DMED from DM-NoED with 87.5% sensitivity and 79.2% specificity. Conclusions: Elevated serum suPAR levels are significantly associated with ED in men with type 2 DM, independent of glycemic control and conventional cardiovascular risk factors. These findings suggest that suPAR may be a promising biomarker for the early detection and risk assessment of ED in diabetic patients. Future prospective studies are needed to confirm its clinical utility. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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33 pages, 726 KB  
Review
Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI
by Sami Alobaidi
Diagnostics 2025, 15(10), 1225; https://doi.org/10.3390/diagnostics15101225 - 13 May 2025
Cited by 22 | Viewed by 8980
Abstract
Chronic kidney disease (CKD) remains a significant global health burden, often diagnosed at advanced stages due to the limitations of traditional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR). This review aims to critically evaluate recent advancements in novel biomarkers, [...] Read more.
Chronic kidney disease (CKD) remains a significant global health burden, often diagnosed at advanced stages due to the limitations of traditional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR). This review aims to critically evaluate recent advancements in novel biomarkers, multi-omics technologies, and artificial intelligence (AI)-driven diagnostic strategies, specifically addressing existing gaps in early CKD detection and personalized patient management. We specifically explore key advancements in CKD diagnostics, focusing on emerging biomarkers—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), soluble urokinase plasminogen activator receptor (suPAR), and cystatin C—and their clinical applications. Additionally, multi-omics approaches integrating genomics, proteomics, metabolomics, and transcriptomics are reshaping disease classification and prognosis. Artificial intelligence (AI)-driven predictive models further enhance diagnostic accuracy, enabling real-time risk assessment and treatment optimization. Despite these innovations, challenges remain in biomarker standardization, large-scale validation, and integration into clinical practice. Future research should focus on refining multi-biomarker panels, improving assay standardization, and facilitating the clinical adoption of precision-driven diagnostics. By leveraging these advancements, CKD diagnostics can transition toward earlier intervention, individualized therapy, and improved patient outcomes. Full article
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16 pages, 640 KB  
Article
The Potential of Cardiac Biomarkers in Differentiating Disease Subtypes in Patients with Systemic Sclerosis: Focus on GDF15, MR-pro ANP, and suPAR
by Olga Gumkowska-Sroka, Anna Chudek, Aleksander Owczarek, Kornelia Kuźnik-Trocha, Kacper Kotyla, Jan Kurdybacha, Jerzy Chudek, Katarzyna Komosińska-Vassev, Katarzyna Winsz-Szczotka, Krystyna Olczyk and Przemysław Kotyla
Int. J. Mol. Sci. 2025, 26(9), 3938; https://doi.org/10.3390/ijms26093938 - 22 Apr 2025
Cited by 1 | Viewed by 1308
Abstract
Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and [...] Read more.
Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and prognosis. While several biomarkers have been proposed to distinguish between these subtypes, none have achieved high sensitivity and specificity. The search for dependable markers that can differentiate between the two primary subtypes of systemic sclerosis continues. To address this gap, our study evaluated the utility of novel cardiac biomarkers, including growth differentiation factor 15 (GDF15), galectin-3, mid-regional pro-atrial natriuretic peptide (MR-proANP), glutathione S-transferase π, mid-regional adrenomedullin, and soluble urokinase plasminogen activator receptor (suPAR), in a cohort of 79 patients with both lcSSc and dSSc subtypes. The results demonstrated a significant elevation of GDF15 (medians: 2.07 vs. 1.10 ng/L; p < 0.001) and MR-proANP (92.55 vs. 65.60 pmol/L; p < 0.05) levels in SSc patients compared to healthy controls. Moreover, GDF15 (1.65 vs. 2.34 ng/mL; p < 0.05), MR-proANP (80.87 vs. 109.27 pmol/L; p < 0.05), and suPAR (1.83 vs. 2.44 ng/mL; p < 0.05) levels were notably higher in patients with dSSc compared to those with lcSSc. In the ROC analysis, only GDF-15, MR-proANP, and suPAR proved to have a statistically significant area under the curve (AUC). Patients with the GDF-15 ≥ 2182 ng/mL, MR-prANP ≥ 85.808 pmol/L, and suPAR ≥ 2.315 ng/mL have more than six-, eight-, and seven-times-higher odds for dcSSc, respectively. These findings highlight the potential of GDF15, suPAR, and MR-proANP as biomarkers for differentiating between the two main subtypes of systemic sclerosis. Full article
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12 pages, 227 KB  
Article
Association of Circulating GDF-15 with Fetal Growth in Gestational Diabetes
by Tiziana Filardi, Enrico Bleve, Valentina Viggiani, Paola Galoppi, Giuseppe Rizzo, Stefania Gorini, Massimiliano Caprio, Antonio Angeloni, Susanna Morano and Emanuela Anastasi
J. Clin. Med. 2025, 14(8), 2764; https://doi.org/10.3390/jcm14082764 - 17 Apr 2025
Cited by 3 | Viewed by 1243
Abstract
Background/Objectives: Growth differentiation factor-15 (GDF-15) is a component of the transforming growth factor beta (TGF-β) family that may act as regulator of inflammation. A possible protective role of GDF-15 against glucose alterations has been hypothesized. The aim of this pilot study was [...] Read more.
Background/Objectives: Growth differentiation factor-15 (GDF-15) is a component of the transforming growth factor beta (TGF-β) family that may act as regulator of inflammation. A possible protective role of GDF-15 against glucose alterations has been hypothesized. The aim of this pilot study was to evaluate the relationship between a circulating concentration of GDF-15 and metabolic/inflammatory parameters, as well as with adverse perinatal outcomes in patients with gestational diabetes mellitus (GDM). Methods: Twenty-four (n = 24) patients with GDM and n = 29 age-matched pregnant women with normal glucose tolerance (NGT) were recruited at the third trimester of gestation. Clinical and biochemical parameters were collected. Serum levels of GDF-15, small dense low density lipoprotein cholesterol (sdLDL), interleukin 6 (IL-6), a Soluble Urokinase Plasminogen Activator Receptor (su-PAR) were measured by an enzyme-linked immunosorbent assay kit. Fetal ultrasound parameters, maternal, delivery, and perinatal outcomes, were assessed. Results: Serum GDF-15 did not differ between GDM and NGT (p = 0.286). However, in linear regression analysis, a significant negative association was observed between GDF-15 and fetal weight percentile at the third trimester, only in patients with GDM (p = 0.013), even after adjustment for age and pre-pregnancy BMI (p = 0.029). GDF-15 positively associated with IL-6, adjusting for pre-pregnancy BMI (p = 0.047). Pregnant women with adverse perinatal outcomes had higher levels of GDF-15 (p = 0.043). In the regression model, higher levels of GDF-15 were associated with an increased likelihood of adverse perinatal outcomes after adjustment for age and pre-pregnancy BMI (p = 0.044). Conclusions: Besides its action as regulator of inflammation, GDF-15 might have a possible protective role against hyperglycemia-related excessive fetal growth in GDM. GDF-15 circulating levels might also be related to adverse perinatal outcomes. Full article
(This article belongs to the Section Obstetrics & Gynecology)
13 pages, 2581 KB  
Article
Evaluation of suPAR as a Key Prognostic Biomarker in Patients with SARS-CoV-2 Pneumonia
by Mónica Piqueras, Paula González-Jiménez, Ana Latorre, Jordi Tortosa-Carreres, Noé Mengot, Ricardo Alonso, Soledad Reyes, Isabel Amara-Elori, Francisco Sanz-Herrero, Rosario Menéndez and Raúl Méndez
Biomedicines 2025, 13(4), 896; https://doi.org/10.3390/biomedicines13040896 - 8 Apr 2025
Viewed by 1224
Abstract
Background/Objectives: SARS-CoV-2 has strained healthcare systems, emphasizing the need for biomarkers to predict disease severity. Recent studies suggest that soluble urokinase plasminogen activator receptor (suPAR) is a promising marker for COVID-19 pneumonia, though its utility alongside the CURB-65 score remains unstudied. This [...] Read more.
Background/Objectives: SARS-CoV-2 has strained healthcare systems, emphasizing the need for biomarkers to predict disease severity. Recent studies suggest that soluble urokinase plasminogen activator receptor (suPAR) is a promising marker for COVID-19 pneumonia, though its utility alongside the CURB-65 score remains unstudied. This study evaluates the prognostic value of suPAR in comparison to leukocyte count and CURB-65, and its potential for enhancing risk stratification in a combined CURB-65 model. Methods: Biomarkers and CURB-65 scores were obtained for 240 immunocompetent patients hospitalised with COVID-19 pneumonia. Intensive care unit admission and in-hospital mortality were assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier analysis. Additionally, a Net Reclassification Improvement (NRI) analysis was performed to evaluate the predictive value of suPAR combined with the CURB-65 score for risk stratification. Results: suPAR demonstrated strong diagnostic accuracy, outperforming lymphocyte count and showing greater precision than the CURB-65 score for ICU admission. Notably, no patient with suPAR < 4 ng/mL experienced the studied outcomes. NRI analysis revealed a significant improvement in risk classification when suPAR was combined with CURB-65. Conclusions: The addition of the suPAR biomarker to the CURB-65 score represents a substantial improvement in the risk classification of patients with COVID-19 pneumonia, with a potential impact on daily clinical practice. Full article
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14 pages, 440 KB  
Article
The Predictive Role of C-Reactive Protein, Leukocyte Cell Count, and Soluble Urokinase Plasminogen Activator Receptor for Pulmonary Sequelae in Hospitalized COVID-19 Survivors: A Prospective Single-Center Cohort Study
by Izzet Altintas, Thomas Kallemose, Mette Bendtz Lindstrøm, Imran Parvaiz, Iben Rokkedal, Lene Juel Rasmussen, Katrine Kjær Iversen, Jesper Eugen-Olsen, Kasper Karmark Iversen, Ejvind Frausing Hansen, Charlotte Suppli Ulrik, Jan Olof Nehlin and Ove Andersen
J. Clin. Med. 2025, 14(5), 1717; https://doi.org/10.3390/jcm14051717 - 4 Mar 2025
Viewed by 1305
Abstract
Background: Pulmonary function impairment significantly affects quality of life, work ability, and healthcare utilization. Among patients with COVID-19, respiratory symptoms vary in severity. This study aimed to assess whether biomarkers related to respiratory function and inflammation at emergency department (ED) admittance can predict [...] Read more.
Background: Pulmonary function impairment significantly affects quality of life, work ability, and healthcare utilization. Among patients with COVID-19, respiratory symptoms vary in severity. This study aimed to assess whether biomarkers related to respiratory function and inflammation at emergency department (ED) admittance can predict long-term pulmonary function impairment in COVID-19 survivors. Methods: This prospective single-center study recruited patients 4–5 months post-COVID-19 infection using consecutive sampling. All attendees at the respiratory outpatient clinic were invited to participate. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide (DLCO), total lung capacity (TLC), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC), were performed, with DLCO < 80% as the key indicator of impairment. Baseline biomarkers—C-Reactive Protein (CRP), leukocyte counts, and soluble urokinase Plasminogen Activator Receptor (suPAR)—were correlated with post-discharge DLCO values. Results: This study enrolled 110 patients with COVID-19; 58.2% were female, the median age was 61.5, and the average BMI was 27.2. Smoking history showed that 53.7% were never smokers, 43.5% were former smokers, and 2.8% were current smokers. A diffusion deficit (DLCO < 80%) was present in 48.6% of patients. Leukocyte counts and suPAR had the highest sensitivity (>0.80) for predicting DLCO impairment but showed low specificity and a positive predictive value (PPV) of around 0.50. However, combining all biomarkers improved prediction accuracy, with a negative predictive value (NPV) of 0.93. Conclusions: The chosen inflammatory biomarkers by themselves had a limited ability to predict long-term pulmonary function impairment in COVID-19 survivors. However, when combined, they demonstrated a high negative predictive value (NPV) for identifying DLCO impairment. This strategy could help clinicians better tailor follow-up care for patients with COVID-19. Full article
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17 pages, 282 KB  
Review
Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients
by Raul Patrascu and Cristina Stefania Dumitru
J. Clin. Med. 2025, 14(5), 1475; https://doi.org/10.3390/jcm14051475 - 22 Feb 2025
Cited by 13 | Viewed by 2723
Abstract
This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, [...] Read more.
This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies. Full article
(This article belongs to the Section Respiratory Medicine)
16 pages, 1498 KB  
Article
Soluble Urokinase Plasminogen Activator Receptor: A Promising Biomarker for Mortality Prediction Among Critical ED Patients
by Piotr Wozniak, Mariusz Sieminski, Jan Pyrzowski, Rafael Petrosjan, Jakub Głogowski-Kulasza and Jakub Leszczyński-Czeczatka
Int. J. Mol. Sci. 2025, 26(4), 1609; https://doi.org/10.3390/ijms26041609 - 13 Feb 2025
Cited by 1 | Viewed by 1173
Abstract
Patients admitted to the emergency department (ED) are a highly diverse group in terms of the risk of death. In overcrowded EDs, it becomes crucial to quickly and reliably estimate the risk of death or significant health deterioration. For this purpose, the concentration [...] Read more.
Patients admitted to the emergency department (ED) are a highly diverse group in terms of the risk of death. In overcrowded EDs, it becomes crucial to quickly and reliably estimate the risk of death or significant health deterioration. For this purpose, the concentration of soluble urokinase plasminogen activator receptor (suPAR) in plasma has been studied in recent years in various patient populations. In the present study, we tested the hypothesis that measuring suPAR upon the ED admission of critically ill patients can identify those at the highest mortality risk. To verify this hypothesis, we analyzed the relationship between suPAR plasma concentration, other biochemical parameters, and Early Warning Scores (EWSs) on admission and survival to hospital discharge. The study group consisted of 61 ED patients with priority 1 in the Manchester Triage System (MTS), excluding patients with illness caused by environmental factors. Positive correlations between suPAR and inflammatory parameters such as CRP and PCT, as well as the warning scales MEWS, MEDS, and qSOFA, were confirmed. Plasma suPAR concentration on admission was found to be a promising predictor of in-hospital mortality. The study indicated the potential prognostic value of suPAR as the mortality risk predictor for a specific population of critically ill ED patients. Full article
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