Tariq U Azam1, Husam R Shadid2, Pennelope Blakely1, Patrick O'Hayer2, Hanna Berlin2, Michael Pan2, Peiyao Zhao3, Lili Zhao3, Subramaniam Pennathur4, Rodica Pop-Busui5, Izzet Altintas6, Jens Tingleff7, Marius A Stauning6, Ove Andersen7, Maria-Evangelia Adami8, Nicky Solomonidi8, Maria Tsilika8, Pinkus Tober-Lau9, Eleni Arnaoutoglou10, Verena Keitel11, Frank Tacke12, Athanasios Chalkias10, Sven H Loosen11, Evangelos J Giamarellos-Bourboulis8, Jesper Eugen-Olsen7, Jochen Reiser13, Salim S Hayek14. 1. Division of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. 2. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. 3. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan. 4. Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. 5. Division of Endocrinology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. 6. Emergency Department, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. 7. Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. 8. 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece. 9. Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. 10. Department of Anesthesiology, School of Health Sciences, Faculty of Medicine, University of Thessaly, Thessaly, Greece. 11. Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany. 12. Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 13. Department of Medicine, Rush University Medical Center, Chicago, Illinois. 14. Division of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan shayek@med.umich.edu.
Abstract
BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.
BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Eva Mittler; Maria Eugenia Dieterle; Lara M Kleinfelter; Megan M Slough; Kartik Chandran; Rohit K Jangra Journal: Adv Virus Res Date: 2019-08-07 Impact factor: 9.937
Authors: T Plesner; E Ralfkiaer; M Wittrup; H Johnsen; C Pyke; T L Pedersen; N E Hansen; K Danø Journal: Am J Clin Pathol Date: 1994-12 Impact factor: 2.493
Authors: Danny J Eapen; Pankaj Manocha; Nima Ghasemzadeh; Riyaz S Patel; Hatem Al Kassem; Muhammad Hammadah; Emir Veledar; Ngoc-Anh Le; Tomasz Pielak; Christian W Thorball; Aristea Velegraki; Dimitrios T Kremastinos; Stamatios Lerakis; Laurence Sperling; Arshed A Quyyumi Journal: J Am Heart Assoc Date: 2014-10-23 Impact factor: 5.501
Authors: Victor G Puelles; Marc Lütgehetmann; Maja T Lindenmeyer; Jan P Sperhake; Milagros N Wong; Lena Allweiss; Silvia Chilla; Axel Heinemann; Nicola Wanner; Shuya Liu; Fabian Braun; Shun Lu; Susanne Pfefferle; Ann S Schröder; Carolin Edler; Oliver Gross; Markus Glatzel; Dominic Wichmann; Thorsten Wiech; Stefan Kluge; Klaus Pueschel; Martin Aepfelbacher; Tobias B Huber Journal: N Engl J Med Date: 2020-05-13 Impact factor: 91.245
Authors: Izzet Altintas; Jesper Eugen-Olsen; Santeri Seppälä; Jens Tingleff; Marius Ahm Stauning; Nora Olsen El Caidi; Sanaá Elmajdoubi; Hejdi Gamst-Jensen; Mette B Lindstrøm; Line Jee Hartmann Rasmussen; Klaus Tjelle Kristiansen; Christian Rasmussen; Jan O Nehlin; Thomas Kallemose; Harri Hyppölä; Ove Andersen Journal: Biomark Insights Date: 2021-08-15
Authors: Markus Bitzer; Wenjun Ju; Lalita Subramanian; Jonathan P Troost; Joseph Tychewicz; Becky Steck; Roger C Wiggins; Debbie S Gipson; Crystal A Gadegbeku; Frank C Brosius; Matthias Kretzler; Subramaniam Pennathur Journal: Am J Physiol Renal Physiol Date: 2022-08-04
Authors: Alexi Vasbinder; Elizabeth Anderson; Husam Shadid; Hanna Berlin; Michael Pan; Tariq U Azam; Ibrahim Khaleel; Kishan Padalia; Chelsea Meloche; Patrick O'Hayer; Erinleigh Michaud; Tonimarie Catalan; Rafey Feroze; Pennelope Blakely; Christopher Launius; Yiyuan Huang; Lili Zhao; Lynn Ang; Monica Mikhael; Kara Mizokami-Stout; Subramaniam Pennathur; Matthias Kretzler; Sven H Loosen; Athanasios Chalkias; Frank Tacke; Evangelos J Giamarellos-Bourboulis; Jochen Reiser; Jesper Eugen-Olsen; Eva L Feldman; Rodica Pop-Busui; Salim S Hayek; Salim S Hayek; Pennelope Blakely; Hanna Berlin; Tariq U Azam; Husam Shadid; Michael Pan; Patrick O'Hayer; Chelsea Meloche; Rafey Feroze; Kishan J Padalia; Elizabeth Anderson; Danny Perry; Abbas Bitar; Rayan Kaakati; Yiyuan Huang; Lili Zhao; Jochen Reiser; Beata Samelko; Alex Hlepas; Priya P Patel; Xuexiang Wang; Jesper Eugen-Olsen; Izzet Altintas; Marius Stauning; Morten Baltzer Houlind; Mette B Lindstrøm; Hejdi Gamst-Jensen; Line Jee Hartmann; Jan O Nehlin; Thomas Kallemose; Imran Parvaiz; Christian Rasmussen; Ove Andersen; Jens Tingleff; Evangelos J Giamarellos-Bourboulis; Maria-Evangelia Adami; Nicky Solomonidi; Maria Tsilika; Maria Saridaki; Vasileios Lekakis; Sven H Loosen; Tom Luedde; Verena Keitel; Athanasios Chalkias; Eleni Arnaoutoglou; Ioannis Pantazopoulos; Eleni Laou; Konstantina Kolonia; Anargyros Skoulakis; Frank Tacke; Pinkus Tober-Lau; Raphael Mohr; Florian Kurth; Leif Erik Sander; Christoph Jochum Journal: Diabetes Care Date: 2022-03-01 Impact factor: 19.112
Authors: Frank L van de Veerdonk; Evangelos Giamarellos-Bourboulis; Peter Pickkers; Lennie Derde; Helen Leavis; Reinout van Crevel; Job J Engel; W Joost Wiersinga; Alexander P J Vlaar; Manu Shankar-Hari; Tom van der Poll; Marc Bonten; Derek C Angus; Jos W M van der Meer; Mihai G Netea Journal: Nat Med Date: 2022-01-21 Impact factor: 87.241