Advancing Multiparametric Kidney Functional Magnetic Resonance Imaging to Identify Kidney Histopathologic Lesions

Patients with chronic kidney disease (CKD) are at increased risks of developing cardiovascular disease, progressing to end stage renal disease, and dying prematurely. New therapies are critically needed to improve outcomes. Through interrogation of kidney biopsy specimens of patients undergoing a research kidney biopsy, The Kidney Precision Medicine Project (KPMP) aims to identify novel pathways and therapeutic targets in patients with CKD. Novel non-invasive tools to phenotype and complement the rich clinical, histopathologic, and molecular data are required. Prior studies implicate decreased kidney perfusion and resultant chronic hypoxia in the pathogenesis of kidney fibrosis. Advancement of novel imaging biomarkers of important physiologic and histopathologic data of the kidney may provide a non-invasive tool to phenotype patients with CKD. Although imaging is underdeveloped in CKD, gadolinium-free multiparametric kidney functional magnetic resonance imaging (fMRI) provides non-invasive assessments of kidney oxygenation, fibrosis, and perfusion that may enhance clinical phenotyping of KPMP participants. Our exciting preliminary data suggest that multiparametric kidney fMRI can be incorporated into multicenter studies with low inter-site variability, and the kidney fMRI-derived measurements have low intra-reader, inter-reader, and intra-participant variability. In addition, the kidney fMRI-derived assessments of hypoxia, fibrosis, and malperfusion are able to differentiate patients with CKD from healthy volunteers and may have prognostic value. In the proposed studies, we will incorporate multiparametric kidney fMRI as a non-invasive tool to phenotype KPMP participants undergoing a research kidney biopsy for CKD. In year 1, we will perform multiparametric kidney fMRI in 15 participants at Boston University Medical Center (BUMC) and demonstrate low intra-reader, inter-reader, and intra-participant variability among kidney fMRI measurements. After the development and implementation of the protocols used to perform multiparametric kidney fMRI at BUMC, we will disseminate the protocols to KPMP. In year 2, we will expand recruitment to 2 additional KPMP sites and perform multiparametric kidney fMRI in 45 additional KPMP participants (n=15 per site). We will also perform a 12 month follow-up multiparametric kidney fMRI in the 15 participants enrolled from BUMC in year 1. In both years, we will test the associations of kidney fMRI-derived assessments of oxygenation, fibrosis, and perfusion with semi-quantitative severity scores of chronic histopathologic lesions. This proposal fosters new collaboration and unites cross-disciplinary investigators experienced in clinical phenotyping of kidney diseases, biomarker development and testing, and imaging. We are committed to collaborative protocol development and cross-disciplinary team science to support the KPMP’s objective to identify novel pathways and therapeutic targets to improve the health of patients with CKD. Execution of the proposed studies will provide a complementary non-invasive phenotyping tool to the KPMP promote the field of non-invasive imaging biomarkers in CKD.