Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection

  • Maryam Aghighi
  • Laura Pisani
  • Ashok J. Theruvath
  • Anne M. Muehe
  • Jessica Donig
  • Ramsha Khan
  • Samantha J. Holdsworth
  • Neeraja Kambham
  • Waldo Concepcion
  • Paul C. Grimm
  • Heike E. Daldrup-Link
Research Article

Abstract

Purpose

To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients.

Procedures

The USPIO ferumoxytol has a long blood half-life and is phagocytosed by macrophages. In an IRB-approved single-center prospective clinical trial, 26 pediatric patients and adolescents (age 10–26 years) with acute allograft rejection (n = 5), non-rejecting allografts (n = 13), and normal native kidneys (n = 8) underwent multi-echo T2* fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5 mg Fe/kg ferumoxytol. T2* relaxation times at 4 h p.i. (perfusion phase) and more than 20 h p.i. (macrophage phase) were compared with biopsy results. The presence of rejection was assessed using the Banff criteria, and the prevalence of macrophages on CD163 immunostains was determined based on a semi-quantitative scoring system. MRI and histology data were compared among patient groups using t tests, analysis of variance, and regression analyses with a significance threshold of p < 0.05.

Results

At 4 h p.i., mean T2* values were 6.6 ± 1.5 ms for native kidneys and 3.9 ms for one allograft undergoing acute immune rejection. Surprisingly, at 20–24 h p.i., one rejecting allograft showed significantly prolonged T2* relaxation times (37.0 ms) compared to native kidneys (6.3 ± 1.7 ms) and non-rejecting allografts (7.6 ± 0.1 ms). Likewise, three additional rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts at later post-contrast time points, 25–97 h p.i. (p = 0.008). Histological analysis revealed edema and compressed microvessels in biopsies of rejecting allografts. Allografts with and without rejection showed insignificant differences in macrophage content on histopathology (p = 0.44).

Conclusion

After ferumoxytol administration, renal allografts undergoing acute rejection show prolonged T2* values compared to non-rejecting allografts. Since histology revealed no significant differences in macrophage content, the increasing T2* value is likely due to the combined effect of reduced perfusion and increased edema in rejecting allografts.

Key words

Kidney allograft rejection MR imaging Iron oxide nanoparticles Ferumoxytol 

Supplementary material

11307_2017_1084_MOESM1_ESM.pdf (258 kb)
ESM 1(PDF 257 kb)

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Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Maryam Aghighi
    • 1
  • Laura Pisani
    • 1
  • Ashok J. Theruvath
    • 1
  • Anne M. Muehe
    • 1
  • Jessica Donig
    • 1
  • Ramsha Khan
    • 1
  • Samantha J. Holdsworth
    • 1
  • Neeraja Kambham
    • 2
  • Waldo Concepcion
    • 3
  • Paul C. Grimm
    • 4
  • Heike E. Daldrup-Link
    • 1
    • 5
  1. 1.Department of Radiology, Pediatric Molecular Imaging in the Molecular Imaging Program at Stanford (@PedsMIPS)Lucile Packard Children’s Hospital, Stanford University School of MedicineStanfordUSA
  2. 2.Department of PathologyStanford UniversityStanfordUSA
  3. 3.Department of SurgeryStanford UniversityStanfordUSA
  4. 4.Department of PediatricsStanford UniversityStanfordUSA
  5. 5.Department of PediatricsLucile Packard Children’s Hospital, Stanford School of MedicineStanfordUSA

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