Performance of a standardized clinical assay for urinary C-C motif chemokine ligand 14 (CCL14) for persistent severe Acute Kidney Injury

Abstract

Background: Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C-motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay. Methods: A second aim of the multicenter Ruby study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received kidney replacement therapy (KRT) or died prior to achieving 72 hours in stage 3 AKI were also considered to have reached the endpoint. Results: A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%, (95%CI 84%-96%)) and 13 ng/ml achieved high specificity (93% (89%-96%)). The cutoff of 1.3 ng/mL identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/mL had an adjusted odds ratio (aOR) of 3.82 (95%CI 1.73-9.12) p=0.001 for the development of persistent severe AKI compared to those with CCL14 ≤ 1.3, while a CCL14 > 13 ng/ml had an aOR of 10.4 (3.89-29.9); p<0.001. Conclusions: Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/mL) allow for the identification of patients at high risk for the development of severe persistent AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.