Supplementary Material for: Urinary cytokeratin 20 predicts severe acute kidney injury and major adverse kidney events in adults undergoing cardiac surgery

Introduction It remains a big challenge to identify patients who are at high risk of developing severe acute kidney injury (AKI) after cardiac surgery. This study investigated the clinical utility of urinary cytokeratin 20 (uCK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of developing severe AKI.

Methods This prospective multicenter cohort study enrolled a Test set comprising 413 patients underwent cardiac surgery in 5 centers and a Validation set enrolling 131 patients at an external center. uCK20 and six reported renal tubular injury biomarkers were measured within 6 hours after cardiopulmonary bypass (CPB). The primary outcome was severe AKI after surgery. The secondary outcome was major adverse kidney events within 30 days (MAKE30).

Results In Test set, 54 patients (13.1%) reached the primary endpoint. Levels of uCK20 peaked at 4 hours after CPB and remained elevated for 5 days after surgery in patients with severe AKI. After multivariable adjustment, the highest tertile of uCK20 was associated with a 67-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, uCK20 at 4 hours after CPB had area under the curves (AUC) of 0.86 (95% confidence interval [CI], 0.81 to 0.91) and 0.85 (95% CI, 0.78 to 0.92), outperforming some reported kidney injury biomarkers. Adding uCK20 to the clinical variables enhanced the predicting ability for severe AKI with AUC of 0.90 (95% CI, 0.85 to 0.94), and largely improved the risk reclassification. The ability of uCK20 in predicting the primary and the secondary outcomes was further confirmed in an external validation set.

Conclusion Urinary CK20 early predicted the risk of severe AKI and MAKE30 with excellent performances in patients undergoing cardiac surgery.