The promise of biomarkers: precision medicine will pave a roadmap for pediatric acute kidney injury management in critically ill children.

Abstract

Acute kidney injury (AKI) is common in critically ill children and neonates and imparts an increased risk for morbidity and mortality. Despite a growing recognition of the untoward consequences of AKI, its management continues to rely on supportive care alone, after numerous clinical trials have failed to identify effective disease-modifying therapies. This failure to advance the field is likely due in large part to the heterogeneity of AKI, which demands a precision approach to diagnosis and management. Despite the emergence of several novel AKI biomarkers with the ability to refine the AKI diagnosis beyond what is afforded by changes in serum creatinine and/or urine output alone, widespread translation of these biomarkers to practice has been limited. In this review, we outline a roadmap for AKI risk-stratification, diagnosis, management, and follow-up that is rooted in precision medicine principles and feasible with the tools currently available in pediatric ICUs. This roadmap highlights the importance of dynamic (as opposed to static) assessment of the critically ill child with, at-risk for, and recovering from AKI, and introduces the concept of theragnostic biomarkers that are both the target of and change with treatment, thus helping guide the therapeutic approach. Finally, we highlight the need for re-defining appropriate endpoints in AKI clinical trials testing the interventions proposed here (and others) to ensure we are identifying treatments that will meaningfully improve outcomes for critically ill children with AKI.