University of Wisconsin–Madison

Determining Acute Rejection versus ATN using Functional MRI

September 2005 to March 2011

In this research, non-invasive MR imaging techniques will be used to evaluate kidney function in the early post-transplantation period. This research will utilize MR perfusion, BOLD MRI, and skGFR in an attempt to differentiate acute rejection from ATN in a population with delayed graft function. In addition to using functional MRI in the diagnosis of transplant dysfunction, we will streamline image analysis to reduce post-processing time and allow widespread clinical application of our techniques. If this research is successful, the results will lead to new understanding of normal kidney function and reveal aspects of the pathophysiologic changes contributing to allograft dysfunction in the early post-transplantation period. Ultimately, the proposed methods could have significant positive impact on the diagnosis of allograft dysfunction and potentially provide a non-invasive means for monitoring treatments aimed at prolonging kidney function.

The goal of this research is to determine if functional magnetic resonance imaging (fMRI) can determine the presence of acute rejection in transplanted kidneys. If MR measures of intrarenal blood flow, oxygen delivery and single kidney glomerular filtration rate (skGFR) can differentiate transplanted kidneys with acute rejection from those with normal function and acute tubular necrosis (ATN) in the early post-operative period, we could avoid biopsy and still target therapy appropriately. At present, the diagnosis of kidney transplant rejection, especially early in the post-transplant time frame, is made via percutaneous biopsy. This procedure is invasive, potentially painful, and can lead to complications, such as bleeding, infection, and rarely loss of the kidney. The theoretical advantages of using MRI to evaluate renal allografts early post-transplant include the ability to diagnose post-transplant conditions non-invasively. Potentially, MRI could be used to screen for acute rejection without having to weigh the risks and benefits of biopsy. This could have an enormous impact in the early post-operative care of transplanted patients. Ultimately this may result in earlier diagnosis and treatment of acute rejection, limiting nephron loss and therefore impacting positively on graft and patient survival.

Kidney transplantation has saved many lives since the first successful transplant more than 50 years ago. Although advances in surgical technique and immunosuppressive therapy have resulted in 1-year survival rates greater than 90 percent, graft dysfunction in the early post-transplant period occurs in up to 30 percent of transplant recipients. This is an important factor in the ultimate fate of the allograft, as acute rejection in those recipients with delayed graft function results in a 5-year graft survival of only 35 percent. This observation alone suggests that early diagnosis of acute rejection episodes is imperative if we are to limit nephron loss and maintain allograph function.

Magnetic Resonance Imaging (MRI) is well-suited for assessing renal transplant anatomy and function. MRI uses non-nephrotoxic contrast agents and has the spatial resolution to independently assess different anatomical regions. New MR techniques, termed functional MRI, can assess the filtration capacity of glomeruli, regional blood flow within the kidney, and the oxygen bioavailability at the tissue level. To date, no other modality can combine techniques to provide such a comprehensive evaluation of the kidney. If MRI can non-invasively identify the underlying cause of dysfunction, we could potentially avoid biopsy and still target therapy appropriately.

The specific aims of this study are: 1) Perform functional MRI studies to measure intrarenal regional blood flow, tissue oxygen bioavailability, and skGFR, in a population of transplant recipients with early impaired graft function. These studies will be performed on the subgroup of transplant recipients, in which clinically, acute rejection needs to be differentiated from ATN, after other causes of early graft dysfunction (EGD) have been excluded. 2) Correlate serum and urine biomarkers of allograft oxidative stress with R2* values obtained during BOLD MRI examination. 3) Clinically indicated percutaneous biopsy will be performed by MRI guidance. Correlate histopathological changes of acute rejection (cellular infiltrates, tubulitis/atrophy, vasculitis, fibrosis) with MR measured intrarenal regional perfusion and oxygen bioavailability.

This project led by: Elizabeth Sadowski, MD