The broad, long-term goal of this multi-disciplinary collaborative of biomedical engineers and physician- scientists is to develop a framework to rapidly and accurately assess the quality of kidneys donated for transplant. Current methods to assess the quality of a donated kidney are derived from population-based surrogates and the limited functional measurements of the individual kidney are only moderately predictive of long-term survival. Additionally, there are no direct, noninvasive clinical measurements of the vasculature or tubulointerstitial compartments. This proposal focuses on the use of novel, noninvasive, MRI-based biomarkers to evaluate human kidneys to individualize and improve the assessment of allograft quality while remaining within the current standards of clinical practice. This work has three Specific Aims: 1) Noninvasively compare MRI-based biomarkers of the glomeruli in human kidneys to metrics currently used in clinical practice (KDPI score and renal resistance by machine perfusion), 2) Noninvasively compare MRI-based biomarkers of microvascular structure in human kidneys to metrics currently used in clinical practice and 3) Develop noninvasive MRI biomarkers of microstructural tubulointerstitial damage that can discriminate reversible from irreversible damage. We will synthesize these aims into a comprehensive view of the renal allograft. The long term goal of this work will be a software platform that integrates all available data (both MRI-based and clinical parameters) from glomerular, vascular, and tubulointerstitial compartments to provide a superior metric of allograft quality. At the conclusion of this project, we will have the first comprehensive, integrated evaluation of the microstructure of the human kidney, powerful data to inform the translation of these MRI-based biomarkers for future studies to improve longevity matching and long-term allograft survival.
The purpose of this project is to develop techniques to detect microstructural changes in intact ex vivo human kidney using MRI. This work will lay the foundation for the use of nanoparticle enhanced-MRI to assess the initial quality of the renal allograft, providing the foundation for the addition of MRI-based biomarkers in the allocation of renal allografts to improve longevity matching and long-term allograft survival.
|Selewski, David T; Hyatt, Dylan M; Bennett, Kevin M et al. (2018) Is acute kidney injury a harbinger for chronic kidney disease? Curr Opin Pediatr 30:236-240|