Clinical journal of the American Society of Nephrology : CJASN · 2026
Validation of Urinary C-C Motif Chemokine Ligand 14 for Persistent Severe AKI Using Clinical Adjudication.
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Kampf J Patrick, Al-Khafaji Ali, Arora Swati, Dhillon Anahat, Heung Michael, Kashani Kianoush, Lopez Marcos G, Szalados James, Tolwani Ashita, Wunderink Richard G, Kellum John A, Zheng Fei, Grosz Sophie, Brossault Ludovic, Coronella June, Octave Lydia, Michel-Busseret Sandrine, Salle Julia de la, Geller Chloé, Koyner Jay L
Аннотация
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.
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.