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

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....

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Published in:Molecular Imaging & Biology Vol. 20; no. 1; pp. 139 - 150
Main Authors: Aghighi, Maryam, Pisani, Laura, Theruvath, Ashok J., Muehe, Anne M., Donig, Jessica, Khan, Ramsha, Holdsworth, Samantha J., Kambham, Neeraja, Concepcion, Waldo, Grimm, Paul C., Daldrup-Link, Heike E.
Format: clinical trial diagnostic images pictorial research tables/charts Journal Article
Published: Springer Nature Feb2018
Online Access:View this record in EBSCOhost
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      dt: Feb2018
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      pub: Springer Nature
      place: New York, New York
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        atl: Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection.
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        au:
          Aghighi, Maryam
          Pisani, Laura
          Theruvath, Ashok J.
          Muehe, Anne M.
          Donig, Jessica
          Khan, Ramsha
          Holdsworth, Samantha J.
          Kambham, Neeraja
          Concepcion, Waldo
          Grimm, Paul C.
          Daldrup-Link, Heike E.
        affil: Department of Radiology, Pediatric Molecular Imaging in the Molecular Imaging Program at Stanford (@PedsMIPS), Lucile Packard Children’s Hospital, Stanford University School of Medicine, 725 Welch Road, 94305, Stanford, CA, USA
      sug:
        subj:
          Kidney Transplantation
          Graft Rejection Immunology
          Allografts
          Receptors, Cell Surface Metabolism
          Adolescence
          Child
          Antigens, Surface Metabolism
          Kinetics
          Graft Rejection
          Magnetic Resonance Imaging
          Young Adult
          Human
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Funding Source
          Clinical Trials
          Adolescent: 13-18 years
          Child: 6-12 years
      ab: 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.
      pubtype: Academic Journal
      doctype:
        clinical trial
        diagnostic images
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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