Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging

Abstract

Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression following renal ischemia-reperfusion injury (IRI): magnetic resonance imaging (MRI) and noninvasive extracellular matrix (ECM) biomarkers. MRI was used to evaluate fibrosis in bilateral IRI in rats after reperfusion at 7, 14, and 21 days. This was performed with 1HT1 and T2* mapping, dynamic contrast-enhanced (DCE)-MRI, and chemical shift imaging (CSI)-23Na. The degradation of laminin gamma-1 chain (LG1M) and type III collagen (C3M) was measured in urine and plasma. Fibrosis was analyzed in tissue using fibronectin (FN) and alpha-smooth muscle actin (α-SMA) using quantitative polymerase chain reaction qPCR and western blotting. We found increased fibrosis 7 days after reperfusion, which dropped to sham levels after 21 days. Single kidney glomerular filtration rate (skGFR), perfusion (DCE-MRI), and total 23Na kidney content correlated positively with fibrotic markers FN and α-SMA as well as noninvasive LG1M and C3M. We showed that novel MRI protocols and ECM markers could track fibrogenic development. This could give rise to a multi-parametric practice to diagnose and assess fibrosis whilst treating kidney disease without using invasive methods.