Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Abstract

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-α, 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.

Keywords: acute renal failure; children; cytokines; heart disease; pediatric nephrology; progression of renal failure.

Graphical abstract

Figure 1.

Flow diagram of patient selection into the study cohort.

Figure 2.

Nine of the 17 biomarkers measured on the first day of AKI were higher in children with AKI progression. Urine and plasma biomarkers were measured on the first day of serum creatinine–defined AKI. The y axis is displayed on a logarithmic scale. Boxes represent the median and interquartile range (25th and 75th percentiles), and whiskers represent the range of values. The asterisks represent a significant difference (P<0.05) in comparison of AKI and non-AKI progression. Cr, creatinine; KIM-1, kidney injury molecule 1; L-FABP, liver fatty acid binding protein; NGAL, neutrophil gelatinase–associated lipocalin.

Figure 3.

Plasma IL-8 had the highest optimism-corrected area under the receiver operating curve (AUC) for the prediction of AKI progression. The adjusted model included the biomarker, cardiopulmonary bypass time, and preoperative eGFR percentile. The AUC with only the clinical variables is 0.67 (95% confidence interval [95% CI], 0.55 to 0.78). The optimism-corrected AUC was estimated using a bootstrap procedure with 1000 replicates. The model fitted using the bootstrap dataset was applied to the original dataset as well as the bootstrap dataset. The average difference in predictive abilities is the optimism. The average optimism in AUCs was subtracted from the apparent AUC to get the optimism-adjusted AUC. Cr, creatinine; KIM-1, kidney injury molecule 1; L-FABP, liver fatty acid binding protein; NGAL, neutrophil gelatinase–associated lipocalin.