Urinary Cytokeratin 20 as a Biomarker for AKI-CKD Transition among Patients with Acute Decompensated Heart Failure and AKI

Background: Predicting the risk of AKI-CKD transition remains a major challenge in management of acute decompensated heart failure and AKI. This study investigated the clinical utility of urinary cytokeratin 20 (CK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of AKI-CKD progression.

Methods: This prospective cohort study included a Test set comprising 279 consecutive hospitalized patients with acute decompensated heart failure and AKI in 5 centers and a Validation set enrolling 206 similar patients at an external center. Urinary CK20 and seven reported renal tubular injury biomarkers at the time of AKI diagnosis were measured. The primary outcome was a composite of AKI-CKD transition 90 days after AKI or all-cause death within 90 days. The secondary outcome was AKI-CKD progression 90 days after AKI.

Results: In the Test set, 115 (41%) patients reached the primary endpoint. Concentrations of urinary CK20 peaked on the day of AKI diagnosis and remained elevated 14 days after AKI. After multivariable adjustment, the highest tertile of urinary CK20 was associated with 21-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, urinary CK20 at the time of AKI diagnosis had area under the receiver-operating characteristic curves (AUC) of 0.82 (95% confidence interval [CI], 0.77-0.87) and 0.81 (95% CI, 0.75-0.87), and outperformed other reported biomarkers reflecting acute tubular injury and the risk of CKD. Adding urinary CK20 to the clinical variables improved the ability for predicting the primary outcome with an AUC of 0.90 (95% CI, 0.85-0.94), and largely improved the risk reclassification. The ability of urinary CK20 in predicting AKI-CKD transition was further confirmed in the Validation set.

Conclusions: Urinary CK20 improved prediction of the risk for transition from AKI to CKD in patients with acute decompensated heart failure and AKI.