Aim There is a high incidence of acute kidney injury (AKI) after cardiac surgery in children, which is associated with significant morbidity and mortality. Serum creatinine (sCr), currently used as an indicator of renal function, only responds to significant kidney injury and following a time delay, resulting in missed and late diagnoses of AKI post-cardiac surgery. Novel biomarkers may provide a more sensitive and timely diagnosis of AKI. The aim of this study was to systematically review the diagnostic value of novel urinary biomarkers of AKI in children undergoing cardiac surgery.
Methods The databases Medline, EMBASE, Cochrane CENTRAL and Web of Science were systematically searched for studies assessing the diagnostic value of any non-creatinine biomarker in identifying AKI in children (<18 years) undergoing any form of cardiac surgery. Screening for eligibility was performed independently by two authors. Random effects meta-analyses were performed where at least three separate studies reported an area under the receiver operator characteristics curve (AUROC) with a 95% confidence interval (CI) or standard error, for a single biomarker.
Results Twenty-five citations were included in the final review. Neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) were the most frequently studied biomarkers, and were the only ones with sufficient data for a meta-analysis. A summary of the pooled AUROC values (with 95% CI) and study heterogeneity (I2) for NGAL, NGAL corrected for urine creatinine (NGAL-uCr) and IL-18 are summarised in the table. There was significant clinical and methodological heterogeneity between included studies, as evidenced by the high I2 values.
Many other biomarkers were only reported in a single, or a few, studies which meant there were insufficient for a meta-analysis. These displayed a wide range of diagnostic utility.
Conclusion NGAL, NGAL-uCr and IL-18 are modest discriminators of AKI when measured within 24 hours of surgery, although other biomarkers (such as KIM-1 and L-FABP) are promising candidates for further research. Larger studies are required to determine biomarker diagnostic/prognostic performance in predicting AKI, and its complications, in children after cardiac surgery.
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