Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Background As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. Methods On the first day of serum creatinine-defined AKI, we measured urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-alpha, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (>= 2 consecutive days). Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.