The objective of this research is to identify whether magnetic resonance (MR) measures of perfusion and oxygen bioavailability can provide a mechanism for assessing progressive changes in kidney function, in vivo, after transplantation. With this knowledge, the potential efficacy of renoprotective therapies using this novel in vivo model can be implemented and assessed.
Many different invasive and non-invasive exams can be used to piece together a picture of renal function. MRI is the only non-invasive method currently available for simultaneous assessment of renal anatomy and physiology. We have developed MRI methods that can provide information regarding renal perfusion and oxygen bioavailability during a single non-invasive exam. To our knowledge, these methods have not yet been used to evaluate the transplanted kidney. Yet, these MRI techniques are ideally suited for assessing kidney transplant grafts. MRI uses a non-nephrotoxic contrast agent, has excellent spatial resolution, and provides unprecedented image contrast for separately evaluating the different anatomical regions.
We anticipate that the results of the study will lead to new understanding of normal transplant kidney physiology and reveal aspects of the pathophysiology contributing to allograft dysfunction over time. The proposed research will also provide a robust method for in vivo monitoring of allograft response to therapies aimed at prolonging function.
The specific aims of this study are: 1) To determine whether MR measured regional intrarenal perfusion and oxygen bioavailability correlate with the onset and evolution of chronic allograft dysfunction during the first 3 years post-transplant (3, 12, 24, and 36 months). 2) To determine whether long-term angiotensin receptor blockade by losartan alters MR measured intrarenal perfusion and oxygen bioavailability in living donor allografts. Living donor transplant recipients will be randomized (1:1) to an initial dose of 50 mg per day of losartan versus no treatment at the time of transplant.