Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance
Condition: Renal Transplant Rejection
Study type: Interventional

Summary: 
      The goal of this study is to develop a non-invasive imaging test for in vivo detection of
      kidney transplant rejection. The hypotheses are that 1) Ferumoxytol-MRI can generate accurate
      estimates of tissue iron concentrations and tissue macrophages. 2) The signal given by a
      renal allograft on Ferumoxytol-MRI demonstrates significant differences between rejected and
      non-rejected transplants.
    

Detailed description: 
      In children with kidney transplants, immunologically mediated rejection is the major cause of
      allograft failure. Thus, the therapeutic success of kidney transplants is highly dependent on
      the ability to avoid rejection during both the acute and chronic phase after transplantation.
      Children with kidney transplants currently undergo at least three routine (protocol) biopsies
      during the first two years after the transplantation in addition to biopsies required to
      investigate deterioration of kidney function. These biopsies are invasive and nearly always
      require general anesthesia, causing anxiety and distress of the patients and their parents,
      as well as significant costs to our health care system. There is currently no non-invasive
      diagnostic tool capable of detecting rejection in vivo. Thus, the goal of this study is to
      develop a non-invasive imaging test for in vivo detection of kidney transplant rejection. The
      investigators propose to accomplish this goal by detecting macrophage infiltration in kidney
      transplants with iron oxide nanoparticle-enhanced MR imaging. Macrophages play a major role
      in transplant rejection. CD68-positive macrophages comprise approximately 50% of the
      infiltrating leukocyte population in renal allograft rejection, they co-localize with areas
      of tissue-damage and fibrosis, and are preponderant in more severe forms of rejection. The
      investigators hypothesize that iron oxide nanoparticle-enhanced MR imaging can detect
      differences in macrophage infiltrations in renal allografts undergoing rejection as opposed
      to allografts without significant rejection. This hypothesis is based on the bio-physical
      properties of intravenously injected superparamagnetic iron oxide nanoparticles, which are
      phagocytosed by tissue macrophages and cause strong signal effects on MR images.

      The specific aims of the study are the following:

      Aim #1. Technical Development of a Quantitative Susceptibility Mapping (QSM)-Sequence for in
      vivo MRI detection and quantification of iron oxide nanoparticle-labeled macrophages.This aim
      will focus on the technical development of Quantitative Susceptibility Mapping (QSM), a novel
      MR imaging pulse sequence that will be used to accurately quantify the tissue concentration
      of free ferumoxytol and ferumoxytol in macrophages in renal allografts. Based on pulse
      sequence optimizations of phantoms with known concentrations of free and cell-bound iron, we
      expect to generate accurate estimates of tissue iron concentrations and macrophages with the
      QSM-MRI method.

      Aim #2. Detect rejection in kidney allografts with ferumoxytol-enhanced MRI. The
      investigators hypothesize that ferumoxytol can detect and quantify macrophages in kidney
      allografts, based upon the observation that iron oxide nanoparticles can be taken up by
      macrophages in malignant tumors. The investigators will evaluate the ability of ferumoxytol
      to map macrophage quantities in renal allografts, with histopathological correlation. We
      expect significantly higher ferumoxytol-MRI enhancement and macrophage quantities in rejected
      allografts compared to non-rejected allografts.
    

Intervention name(s): Feraheme; MRI-GE Healthcare 3 Tesla magnet
Intervention type(s): Drug; Other
Intervention description(s): Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging; All patients will undergo
Other intervention name(s): Ferumoxytol; Magnetic Resonance Imaging; MR Imaging
Intervention MeSH terms: Ferrosoferric Oxide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: kidney; transplant; rejection; Feraheme; ferumoxytol