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Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection
Maryam Aghighi1, Laura Pisani1, Ashok J Theruvath1
1Department 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, Stanford, 94305, CA, USA.
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.
Insights
Ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced MRI can detect kidney transplant rejection in pediatric patients. Prolonged T2* values in USPIO-enhanced MRI indicate allograft rejection, likely due to perfusion and edema.
Area of Science:
- Radiology
- Nephrology
- Immunology
Background:
- Kidney transplantation is crucial for pediatric end-stage renal disease.
- Accurate detection of allograft rejection is vital for patient outcomes.
- Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) offer potential for enhanced MRI contrast.
Purpose of the Study:
- To evaluate the efficacy of USPIO-enhanced MRI in detecting allograft rejection in pediatric kidney transplant recipients.
- To determine if USPIO-enhanced MRI can differentiate between rejecting and non-rejecting allografts.
- To correlate MRI findings with histological biopsy results.
Main Methods:
- A prospective clinical trial involving 26 pediatric patients and adolescents.
- USPIO ferumoxytol (5 mg Fe/kg) administered intravenously.
- Multi-echo T2* fast spoiled gradient-echo MRI performed at 4 hours and >20 hours post-injection.
- Comparison of T2* relaxation times with Banff criteria and CD163 immunostains.
Main Results:
- Rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts and native kidneys at later time points (20-97 hours post-injection).
- Histological analysis of rejecting allografts revealed edema and compressed microvessels.
- No significant difference in macrophage content was observed between rejecting and non-rejecting allografts.
Conclusions:
- USPIO-enhanced MRI can detect acute allograft rejection in pediatric kidney transplant patients.
- Prolonged T2* values post-ferumoxytol administration are indicative of rejection.
- The observed MRI changes are likely attributed to reduced perfusion and increased edema in rejecting allografts.