@article{4cc9b552d0e546daa1370ff297df363a,
title = "Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study",
abstract = "Purpose: The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI). Methods: The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724). Results: 364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C–C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78–0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75. Conclusion: Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.",
keywords = "Biomarkers, C-C motif chemokine ligand 14 (CCL14), KIM-1 (kidney injury molecule-1), NGAL (Neutrophil gelatinase-associated lipocalin), Persistent acute kidney injury, Plasma cystatin C",
author = "{The RUBY Investigators} and Eric Hoste and Azra Bihorac and Ali Al-Khafaji and Ortega, {Luis M.} and Marlies Ostermann and Michael Haase and Kai Zacharowski and Richard Wunderink and Michael Heung and Matthew Lissauer and Self, {Wesley H.} and Koyner, {Jay L.} and Honore, {Patrick M.} and Prowle, {John R.} and Michael Joannidis and Forni, {Lui G.} and Kampf, {J. Patrick} and Paul McPherson and Kellum, {John A.} and Chawla, {Lakhmir S.} and Kyle Gunnerson and Daniel Herr and Danielle Davison and Antonio Artigas and Rebecca Schroeder and Sevag Demirjian and Luke Hodgson and Scott Wilber and Frey, {Jennifer A.} and Ian Reilly and Jing Shi and Thomas Kwan",
note = "Funding Information: RUBY Investigators: Eric Hoste (Ghent University Hospital, Ghent University Ghent, Belgium), Azra Bihorac (Department of Medicine, University of Florida, Gainesville, FL, USA), Ali Al-Khafaji (Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA), Luis M. Ortega (Allegheny General Hospital, Pittsburgh, PA, USA), Marlies Ostermann (King{\textquoteright}s College London, Guy{\textquoteright}s & St Thomas{\textquoteright} Hospital, London, UK), Michael Haase (MVZ Diaverum Am Neuen Garten, Potsdam; Medizinische Fakult{\"a}t, Otto-von-Guericke Universit{\"a}t Magdeburg, Magdeburg, Germany), Kai Zacharowski (University Hospital Frankfurt, Goethe University, Frankfurt, Germany), Richard Wunderink (Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago IL, USA), Michael Heung (Division of Nephrology, Department of Medicine University of Michigan, Ann Arbor, MI), Kyle Gunnerson (Department of Emergency Medicine, MCIRCC, Michigan Medicine, Ann Arbor, MI), Matthew Lissauer (Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901), Daniel Herr (Dept of internal medicine. University of Maryland), Wesley H. Self (Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Jay L. Koyner (Section of Nephrology, Department of Medicine, University of Chicago, Chicago IL, USA), Patrick M. Honore (Univeristy Hospital Brussels, Brussels, Belgium), John R. Prowle (Royal London Hospital, Barts Health NHS Trust. London, UK), Danielle Davison (Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington, D.C. USA), Antonio Artigas (Critical Center, Corporaci{\'o}n Sanitaria Universitaria Parc Tauli, CIBER Enfermedades Respiratorias, Autonomous University of Barcelona), Michael Joannidis (Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria), Rebecca Schroeder (Duke University School of Medicine, Durham, NC, USA), Sevag Demirjian (Department of Nephrology, Cleveland Clinic Foundation, Cleveland, OH, USA), Lui G. Forni (Department of Clinical & Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK), Luke Hodgson (Worthing Hospital, Worthing, U.K), Scott T. Wilber (Northeast Ohio Medical University, Rootstown, Ohio), Jennifer A. Frey (Summa Health System, Akron, Ohio, USA), Ian Reilly (Scripps Medical Center, San Diego, CA, USA), Jing Shi (Walker Biosciences, Carlsbad, CA, USA), J. Patrick Kampf (Astute Medical, Inc., San Diego, CA, USA), Thomas Kwan (Astute Medical, Inc., San Diego, CA, USA), Paul McPherson (Astute Medical, Inc., San Diego, CA, USA), John A. Kellum (Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh PA, USA), and Lakhmir S. Chawla (Department of Medicine, Veterans Affairs Medical Center, San Diego, CA, USA) Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = may,
day = "1",
doi = "10.1007/s00134-019-05919-0",
language = "English (US)",
volume = "46",
pages = "943--953",
journal = "Intensive Care Medicine",
issn = "0342-4642",
publisher = "Springer Verlag",
number = "5",
}