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- Title
Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection.
- 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.
- Abstract
<bold>Purpose: </bold>To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients.<bold>Procedures: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Subjects
GRAFT rejection; HOMOGRAFTS; IRON oxide nanoparticles; SUPERPARAMAGNETIC materials; KIDNEY transplantation; ANTIGENS; CELL receptors; CLINICAL trials; COMPARATIVE studies; DYNAMICS; MAGNETIC resonance imaging; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH funding; EVALUATION research
- Publication
Molecular Imaging & Biology, 2018, Vol 20, Issue 1, p139
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-017-1084-8