IMPAKT Study: Imaging Modalities in Pediatric Assessments of Kidney Transplants

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PROJECT SUMMARY/ ABSTRACT The overarching objectives of this proposal are to investigate whether novel quantitative MRI and ultrasound imaging parameters can reliably detect kidney transplant injury that indicates risk of allograft failure in children. Children with end-stage kidney disease (ESKD) have a mortality rate 30 times higher than children without it. As kidney transplantation provides a significant survival advantage over dialysis, children with ESKD often require multiple kidney allografts over their lifespan. Each transplant increases surgical, immunological, and oncogenic risk. Kidney allograft injury results from inflammatory, infectious, vascular, and fibrotic changes that can ultimately result in allograft failure. A major limitation to promoting long-term allograft survival is the lack of non- invasive diagnostic and prognostic biomarkers to reliably detect early injury in the allograft. This proposal seeks to develop magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) biomarkers to measure inflammation of kidney transplant in children. Currently, kidney allograft biopsy is the gold standard to diagnose such changes, but is invasive and not free of complications, which limits its use. Identifying such markers will allow us to implement individualized interventions to improve allograft survival and decrease unnecessary biopsies. Aim 1 will determine advanced MRI and CEUS parameters that associate with histopathological total inflammation Banff score and Chronic Allograft Damage Index (CADI) score. Aim 2 will identify novel MRI and CEUS parameters that predict change of eGFR in pediatric kidney transplant recipients at 6-24 months post-transplantation. The results will inform the field of novel non-invasive imaging biomarkers in pediatric kidney transplantation. Complementary to this investigation I plan to acquire further training in 1) conventional and CEUS research imaging acquisition and analysis, 2) MRI research data acquisition and analysis, 3) design and implementation of biomedical imaging based patient-oriented research studies, and 4) acquire leadership skills through a professional development plan in the rigorous research environment of Children’s Hospital of Philadelphia and University of Pennsylvania. To accomplish these goals, I have assembled a multi-disciplinary mentoring/advisory team of experts in clinical nephrology patient-oriented research (Primary mentor, Susan Furth, MD, PhD), MRI clinical and translational research studies (Timothy Roberts, MD, PhD; Suraj Serai, PhD), CEUS (Chandra Seghal, PhD; Susan Back, MD; Anush Sridharan, PhD), pediatric kidney transplantation biomarkers (Sandra Amaral, MD, MHS), multinational collaborative networks (Gregory Tasian, MD, MSCE), kidney disease statistical methods (Jarcy Zee, PhD), and patient-oriented imaging research (Kassa Darge, MD, PhD; Erum Hartung, MD, MSTR; Hansel Otero, MD). The proposed research, along with the structured mentoring, coursework, and training that comprise my career development plan, will provide me with the skills and experience necessary to ensure my success as an independent investigator with a unique skill set in developing imaging biomarkers for kidney transplantation.