Multiparametric Functional Magnetic Resonance Imaging (MRI) for Early Detection of Hypoxia Induced Acute Kidney Injury (AKI) and Kidney Transplant Rejection in Mice.

Abstract

Background - Acute kidney injury (AKI) is common complication after solid organ transplantation and contributes also to delayed graft function after kidney transplantation. Detection of AKI oftentimes is delayed due to limited sensitivity of diagnostic methods. Here, we present new magnetic resonance imagining (MRI) techniques to detect and to monitor experimental AKI and acute kidney transplant rejection. Methods-Renal ischemia reperfusion injury (IRI) was induced in mice by transient unilateral clamping of the left renal pedicle. In a kidney transplant model for allogenic rejection C57Bl/6 mice donor kidneys were transplanted in Balb/C mice and compared to isogenic transplantation. MRI was performed prior to surgery and at different time points thereafter (day 1, 7, 14, 21, 28) and renal perfusion, tissue edema and apparent diffusion coefficients (ADC) were determined. Renal morphology, glomerular filtration rate, renal blood flow and inflammatory cell infiltration were investigated. Results -AKI induced renal perfusion impairment was detectable 24h after injury and deteriorated until day 7. Edema formation and changes in ADC correlated with inflammation and fibrosis. At histology a dramatic increase of infiltrating cells was observed. Reduction of MRI measured renal perfusion was verified by PAH clearance to investigate systemic renal blood flow (RBF). The MRI techniques also were applicable for kidney transplant evaluation and showed clearly that allogenic rejection correlated with severe and progressive renal perfusion impairment and edema formation. Conclusion - Our study proves that multiparametric functional MRI is a new and safe technique for early detection of AKI and transplant rejection which offers new perspectives in renal imaging in transplantation medicine.