Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study

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 \u3e 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