Abstract
BACKGROUNDIdentifying patients with acute kidney injury (AKI) at high risk of chronic kidney disease (CKD) progression remains a challenge.METHODSKidney transcriptome sequencing was applied to identify the top upregulated genes in mice with AKI. The product of the top-ranking gene was identified in tubular cells and urine in mouse and human AKI. Two cohorts of patients with prehospitalization estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 who survived over 90 days after AKI were used to derive and validate the predictive models. AKI-CKD progression was defined as eGFR < 60 mL/min/1.73 m2 and with minimum 25% reduction from baseline 90 days after AKI in patients with prehospitalization eGFR ≥ 60 mL/min/1.73 m2. AKI-advanced CKD was defined as eGFR < 30 mL/min/1.73 m2 90 days after AKI in those with prehospitalization eGFR 45-59 mL/min/1.73 m2.RESULTSKidney cytokeratin 20 (CK20) was upregulated in injured proximal tubular cells and detectable in urine within 7 days after AKI. High concentrations of urinary CK20 (uCK20) were independently associated with the severity of histological AKI and the risk of AKI-CKD progression. In the Test set, the AUC of uCK20 for predicting AKI-CKD was 0.80, outperforming reported biomarkers for predicting AKI. Adding uCK20 to clinical variables improved the ability to predict AKI-CKD progression, with an AUC of 0.90, and improved the risk reclassification.CONCLUSIONThese findings highlight uCK20 as a useful predictor for AKI-CKD progression and may provide a tool to identify patients at high risk of CKD following AKI.FUNDINGNational Natural Science Foundation of China, National Key R&D Program of China, 111 Plan, Guangdong Key R&D Program.