Validation of Urinary C-C Motif Chemokine Ligand 14 for Persistent Severe AKI Using Clinical Adjudication

Background: Urinary C-C motif chemokine ligand 14 (CCL14) has been demonstrated to prognosticate persistent severe acute kidney injury (PS-AKI) in patients with established AKI. We sought to validate the performance of CCL14 among intensive care unit (ICU) patients, at previously established cutoffs of 1.3 and 13 ng/mL. Methods: The Diamond Study was a multi-center prospective observational study of ICU patients with KDIGO Stage 2 or 3 AKI within the last 36 hours. Urine was collected at enrollment for CCL14 measurement. The primary study endpoint was the development of PS-AKI (Stage 3, lasting for ≥72 hours) as determined by a clinical adjudication committee consisting of three nephrologists with expertise in AKI. Results: We enrolled 476 patients with CCL14 measurements and 151 (32%) were adjudicated to have PS-AKI. At enrollment, PS-AKI patients had higher APACHE III scores and more Stage 3 AKI (p<0.002 for both). Ninety-five (20%) patients received kidney replacement therapy (KRT), 98 (21%) died, and 155 (33%) received KRT and/or died within 30 days. The area under the receiver operating characteristic curve (95% CI) for CCL14’s prediction of PS-AKI was 0.70 (0.65-0.76). The sensitivity at the 1.3 ng/mL cutoff was 78.1% (70.9%-84.0%), while the specificity was 49.8% (44.4%-55.3%). For every 1 ng/mL increase in CCL14, there was a 6% higher rate of KRT initiation; with values above 13 ng/mL having a hazard ratio (95%CI) of 5.70 (3.22-10.11) for need for KRT and 3.50 (2.19-5.60) for need for KRT or death relative to values ≤1.3 ng/mL (p<0.001 for all). Conclusions: In ICU patients with Stage 2 or 3 AKI, urinary CCL14 is associated with a higher risk of PS-AKI, including KRT initiation and death. Future efforts to treat AKI could be enriched using CCL14 to target those at high risk for PS-AKI.