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Published on: February 15, 2022
A Precision Medicine Approach to Biomarker Utilization in Pediatric Sepsis-Associated Acute Kidney Injury
James D Odum1, Hector R Wong1,2, Natalja L Stanski1,2
1Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Insights
Identifying sepsis-associated acute kidney injury (SA-AKI) in children is crucial. A new framework focusing on individual inflammatory responses may improve prediction, diagnosis, and treatment of SA-AKI.
Area of Science:
- Pediatric critical care medicine
- Nephrology
- Immunology
Background:
- Sepsis is a major cause of death in critically ill children.
- Acute kidney injury (AKI) is a common complication of sepsis, worsening outcomes.
- Current treatments for sepsis-associated AKI (SA-AKI) are limited to supportive care and prevention.
Purpose of the Study:
- To review current biomarkers for SA-AKI in pediatric sepsis.
- To propose a novel framework for SA-AKI biomarker discovery and use.
- To emphasize the role of the host immune response in SA-AKI pathophysiology.
Main Methods:
- Literature review of existing SA-AKI biomarkers.
- Analysis of the pathophysiology of SA-AKI, focusing on inflammation.
- Proposal of a new conceptual framework for biomarker development.
Main Results:
- Current biomarkers for SA-AKI in pediatric sepsis have shown variable success.
- The host immune response is a key factor in SA-AKI development.
- A precision medicine approach is needed for SA-AKI management.
Conclusions:
- A new framework integrating individual inflammatory responses is proposed for SA-AKI.
- This approach aims to improve prediction and diagnosis of SA-AKI.
- Understanding the immune response may reveal new therapeutic targets for SA-AKI.
Abstract:
Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner - as a direct consequence of the individual patient's sepsis inflammatory response - will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.
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