Prospective Cohort Study of Soluble Urokinase Plasminogen Activation Receptor and Cardiovascular Events in Patients With CKD
Year: 2023
Type: article
Study design: Observational Study
Abstract: Introduction Soluble urokinase plasminogen activation receptor (suPAR) is an immune-derived pathogenic factor for kidney and atherosclerotic disease. Whether the association between suPAR and cardiovascular (CV) outcomes is dependent on the severity of underlying kidney disease is unclear. Methods We measured serum suPAR levels in 4994 participants (mean age 60 years; 60% men; 36% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) 49 ml/min per 1.73 m 2 , SD 18) of the German Chronic Kidney Disease (GCKD) cohort and examined its association with all-cause death, CV death, and major CV events (MACE) across the range of eGFR and urine albumin-to-creatinine ratio (UACR). Results The median suPAR level was 1771 pg/ml (interquartile range [IQR] 1447–2254 pg/ml). SuPAR levels were positively and independently correlated with age, eGFR, UACR, and parathyroid hormone levels. There were 573 deaths, including 190 CV deaths and 683 MACE events at a follow-up time of 6.5 years. In multivariable analyses, suPAR levels (log 2 ) were associated with all-cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.21–1.53), CV death (HR 1.27, 95% CI 1.03–1.57), and MACE (HR 1.13, 95% CI 1.00–1.28), and were not found to differ according to diabetes mellitus status, baseline eGFR, UACR, or parathyroid hormone levels. In mediation analysis, suPAR's direct effect on all-cause death, CV death, and MACE accounted for 77%, 67%, and 60% of the total effect, respectively; whereas the effect mediated through eGFR accounted for 23%, 34%, and 40%, respectively. Conclusion In a large cohort of individuals with chronic kidney disease (CKD), suPAR levels were associated with mortality and CV outcomes independently of indices of kidney function, consistent with its independent role in the pathogenesis of atherosclerosis.
Source: Kidney International Reports
Authors: Claudia Sommerer, Sandra Müller-Krebs, Jennifer Nadal, Ulla T. Schultheiss, Nele Friedrich, Matthias Nauck, Matthias Schmid, Christian Nußhag, Jochen Reiser, Kai-Uwe Eckardt, Martin Zeier, Salim S. Hayek, Kai-Uwe Eckardt, Heike Meiselbach, Markus P. Schneider, Mario Schiffer, Hans-Ulrich Prokosch, Barbara Bärthlein, Andreas Beck, Detlef Kraska, André Reis, Arif B. Ekici, Susanne Becker, Ulrike Alberth-Schmidt, Sabine Marschall, Eugenia Schefler, Anke Weigel, Gerd Walz, Anna Köttgen, Ulla T. Schultheiß, Fruzsina Kotsis, Simone Meder, Erna Mitsch, Ursula Reinhard, Jürgen Floege, Turgay Saritas, Elke Schaeffner, Seema Baid-Agrawal, Kerstin Theisen, Kai Schmidt-Ott, Martin Zeier, Claudia Sommerer, Mehtap Aykac, Gunter Wolf, Martin Busch, Rainer Paul, Thomas Sitter, Christoph Wanner, Vera Krane, Antje Börner-Klein, Britta Bauer, Florian Kronenberg, Julia Raschenberger, Barbara Kollerits, Lukas Forer, Sebastian Schönherr, Hansi Weissensteiner, Peter Oefner, Wolfram Gronwald, Matthias Schmid, Jennifer Nadal
Institutions: Heidelberg University, University Hospital Heidelberg, University Hospital Bonn, Institut für Medizinische Biometrie, Informatik und Epidemiologie, University of Freiburg, University Medical Center Freiburg, Universitätsmedizin Greifswald, Universität Greifswald, German Centre for Cardiovascular Research, Rush University Medical Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Charité - Universitätsmedizin Berlin, University of Michigan
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,625
Funders: Gilead Sciences, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, Medizinischen Hochschule Hannover, Universität Regensburg, RWTH Aachen University, Julius-Maximilians-Universität Würzburg, Medizinische Universität Innsbruck, Universität Innsbruck, Bundesministerium für Bildung, Wissenschaft und Forschung, KfH-Stiftung Präventivmedizin, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G3803894709, Extracorporeal SuPAR Extraction to Prevent COVID-19-associated Acute Kidney Injury, Verbundprojekt: Beobachtungsstudie zur chronischen Niereninsuffizienz in Deutschland (GCKD) Studie - TP2 Regionalzentren (anteilig), Verbundprojekt: Beobachtungsstudie zur chronischen Niereninsuffizienz in Deutschland (GCKD-Studie) - TP2 Regionalzentren (anteilig) und TP4 Substudie Koronarkalzifizierung (anteilig), Verbundprojekt: Beobachtungsstudie zur chronischen Niereninsuffizienz in Deutschland (GCKD Studie) - TP3 Proteomanalytik, Verbundprojekt: Beobachtungsstudie zur chronischen Niereninsuffizienz in Deutschland (GCKD Studie) - TP2 Regionalzentren (anteilig), G8769141367
OpenAlex ID: W4386570984