Developing a Precision Medicine Approach to Pediatric Sepsis-Associated Acute Kidney Injury: Identification of Unique Subphenotypes and Strategies for Bedside Implementation

项目总结/文摘:

PROJECT SUMMARY/ABSTRACT: Septic shock impacts 10% of children admitted to the pediatric intensive care unit, 25% of whom die. Outcomes are particularly poor in those who suffer sepsis-associated acute kidney injury (SA-AKI), a heterogeneous syndrome driven by the dysregulated host immune response to infection, and for which limited treatment options exist. Informed by existing adult literature and a strong foundation of preliminary data, Dr. Stanski’s proposal seeks to develop a precision medicine approach to management of these high risk children with septic shock and SA-AKI, by leveraging clinical and biomarker data to identify unique SA-AKI subphenotypes that may inform vasoactive medication selection at the bedside. The results from these studies will guide future prospective work to identify treatment strategies for pediatric SA-AKI, and improve outcomes for children with septic shock as a whole. Candidate: Dr. Natalja Stanski is an Assistant Professor of Pediatric Critical Care Medicine at the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center (CCHMC). She has a strong early track record of patient-oriented research in the areas of acute kidney injury and sepsis precision medicine, focusing on identifying strategies to characterize syndrome heterogeneity. Dr. Stanski’s long- term goal is to become an independent physician-scientist leading precision-medicine informed patient-oriented research to improve outcomes for children with sepsis and SA-AKI. As such, her training goals as part of this award include gaining advanced knowledge in the following areas: design and conduct of patient-oriented research (including clinical trials), implementation science and qualitative research methodologies, advanced biostatistics (including techniques for cluster analysis), and content expertise in precision medicine, sepsis and SA-AKI. To accomplish these goals, Dr. Stanski’s career development plan includes formal coursework in advanced biostatistics, clinical trial management, implementation science and qualitative research; individualized expert mentoring; training by expert consultants; and completion of the proposed research aims. Research: The aims of this study are: 1) to use cluster analysis methodology to identify novel pediatric SA-AKI clinical subphenotypes and describe their associations with outcomes and serum biomarker profiles, and 2) to use Implementation Mapping to develop a rigorous, theory-based implementation plan for personalized vasoactive selection in children with septic shock and SA-AKI. This application leverages the outstanding research infrastructure at CCHMC, and the support of a formidable expert mentorship, consultant and collaborator team. Specifically, Dr. Stanski’s access to the existing large patient datasets and biorepositories necessary to conduct this important work makes her uniquely suited to complete her proposed research aims. The support and training provided by this K23 will leave Dr. Stanski well-positioned to achieve her long-term goal of research independence, and the preliminary data generated will provide the foundation for a feasible precision medicine approach to SA-AKI management that is needed to improve outcomes in pediatric septic shock.