Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation.

Kathleen Cantow,Sonia Waiczies,Bert Flemming,Andreas Pohlmann,Thoralf Niendorf,Fabienne Ferrara,Dirk Grosenick,Erdmann Seeliger

doi:10.1038/srep29965

Abstract

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction.

Highlights

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI)
Ferumoxytol consists of iron oxide nanoparticles encapsulated by a polyglucose sorbitol carboxymethylether coating that is approved in the USA and the EU as intravascular iron supplementation therapy for patients with iron deficiency anemia related to chronic kidney disease (CKD)
The surgical preparation and physiological experimentation to study regulation of renal hemodynamics and oxygenation was performed in 10 anesthetized rats, yet for anatomical and/or technical reasons, reliable data on renal blood flow (RBF), cortical Laser-flux, and cortical pO2 could only be obtained in 9 rats, and data on medullary Laser-flux and medullary pO2 in 8 rats

Summary

Introduction

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). Ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction. Applications range from angiography of various vascular beds including the renal vasculature to the assessment of the blood volume fraction[1,2,3,5,6,7] The latter is of relevance for blood oxygenation level-dependent (BOLD) MRI, because the effective relaxation time T2*is linked to the amount of deoxygenated hemoglobin per tissue volume (voxel). Hypotensive episodes were reported in three recent studies in children and young adults in whom ferumoxytol was used as MR contrast agent[16,17,18] In one of these studies, serum creatinine and urea concentrations were measured and found unaltered by ferumoxytol[16]. Such data are urgently needed, because, according to basic methodologic principles, it must be ascertained that a method intended to measure a certain variable does not per se alter this variable

Methods

Results

Conclusion