Kidney transplantation is the most cost-effective therapy for end-stage renal disease. However, acute rejection (AR), delayed graft function (DGF) and immunosuppressive drug nephrotoxicity remain common complications. It is important to distinguish AR from DGF and immunosuppressive drug toxicity, since the therapeutic options for each may differ significantly. Bioassays of serum creatinine, blood urea nitrogen (BUN), and urine output may indicate the occurrence of renal dysfunction but not the type. Biopsy remains the gold standard, but is invasive and highly localized. Renal perfusion can be a sensitive and distinguishing parameter of the rejection process. AR is characterized by a marked, sudden decrease in both perfusion and function of the kidney while DGF and immunosuppressive drug toxicity typically show normal or slightly reduced perfusion in qualitative MRI studies. Perfusion MRI can identify spatial and temporal perfusion changes in the kidney that will aid in the diagnosis of AR.
The specific aims of our research are: 1) to develop and improve non-invasive multi-slice ASL perfusion MRI using simultaneous proximal and distal irradiation (SPDI) and 2) to use SPDI to measure perfusion rates in healthy and transplant volunteers. SPDI labels endogenous arterial water using a variant of continuous arterial spin labeling (CASL). MR images will be acquired with ultra-fast snapshot techniques (e.g., EPI). The research is designed to test the sensitivity and reliability of SPDI for detecting regional perfusion variations, and compare SPDI with quantitative multi-slice dynamic susceptibility contrast (DSC) measurements. The perfusion MRI technique will be tested in healthy and transplanted kidneys twice during the first three months following transplantation. The condition of the transplanted kidneys will be categorized (e.g., normal, AR, and DGF) based on bioassay and biopsy results. The study will test the hypotheses that 1) multi-slice MRI using SPDI can reliably and accurately measure renal cortical perfusion rates in humans with a systematic error of less than 0.6 ml/g-rain, and 2) changes in renal cortical perfusion rates of greater than 1 ml/g-min in the period within 3 months after transplantation can be used in association with MR angiographic, biochemical, and biopsy data to distinguish AR from DGF and immunosuppressive drug toxicity.
