Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study
Eric Hoste, Azra Bihorac, Ali Al-Khafaji, Luis M Ortega, Marlies Ostermann, Michael Haase, Kai Zacharowski, Richard Wunderink, Michael Heung, Matthew Lissauer, Wesley H Self, Jay L Koyner, Patrick M Honore, John R Prowle, Michael Joannidis, Lui G Forni, J Patrick Kampf, Paul McPherson, John A Kellum, Lakhmir S Chawla, RUBY Investigators, Eric Hoste, Azra Bihorac, Ali Al-Khafaji, Luis M Ortega, Marlies Ostermann, Michael Haase, Kai Zacharowski, Richard Wunderink, Michael Heung, Kyle Gunnerson, Matthew Lissauer, Daniel Herr, Wesley H Self, Jay L Koyner, Patrick M Honore, John R Prowle, Danielle Davison, Antonio Artigas, Michael Joannidis, Rebecca Schroeder, Sevag Demirjian, Lui G Forni, Luke Hodgson, Scott Wilber, Jennifer A Frey, Ian Reilly, Jing Shi, J Patrick Kampf, Thomas Kwan, Paul McPherson, John A Kellum, Lakhmir S Chawla, Eric Hoste, Azra Bihorac, Ali Al-Khafaji, Luis M Ortega, Marlies Ostermann, Michael Haase, Kai Zacharowski, Richard Wunderink, Michael Heung, Matthew Lissauer, Wesley H Self, Jay L Koyner, Patrick M Honore, John R Prowle, Michael Joannidis, Lui G Forni, J Patrick Kampf, Paul McPherson, John A Kellum, Lakhmir S Chawla, RUBY Investigators, Eric Hoste, Azra Bihorac, Ali Al-Khafaji, Luis M Ortega, Marlies Ostermann, Michael Haase, Kai Zacharowski, Richard Wunderink, Michael Heung, Kyle Gunnerson, Matthew Lissauer, Daniel Herr, Wesley H Self, Jay L Koyner, Patrick M Honore, John R Prowle, Danielle Davison, Antonio Artigas, Michael Joannidis, Rebecca Schroeder, Sevag Demirjian, Lui G Forni, Luke Hodgson, Scott Wilber, Jennifer A Frey, Ian Reilly, Jing Shi, J Patrick Kampf, Thomas Kwan, Paul McPherson, John A Kellum, Lakhmir S Chawla
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.
Conflict of interest statement
Jing Shi, John Kellum, Jay Koyner, and Lakhmir Chawla report receiving consulting fees from Astute Medical. Paul McPherson, Patrick Kampf, and Thomas Kwan are employees of Astute Medical, a bioMérieux subsidiary. Marlies Ostermann reports receiving consulting fees from bioMérieux. Lui Forni reports receiving consulting fees from Ortho Clinical Diagnostics. John Prowle reports receiving research support from bioMérieux. Michael Haase reports receiving lecture fees and travel cost reimbursement from Abbott Diagnostics, Astute Medical, FastBiomedical, and Alere.
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Source: PubMed