Acute kidney function and morphology following topload administration of recombinant hemoglobin solution

Abstract

There is a 0.138% incidence of adverse reactions related to blood transfusion. Transfusion-related acute lung injury, immunosuppression, fever, pathogen transmission, and hemolytic transfusion reactions are the most common ones. Synthetic oxygen carriers have been developed to deal with blood shortages and for use in the field where stored blood was not available. They were also designed to be pathogen free, including unknown viruses. In this study, we used Male Golden Syrian Hamsters implemented with a dorsal window chamber to determine how infusion of three different, genetically crosslinked recombinant acellular hemoglobin (rHb) solutions with different oxygen affinities and nitric oxide kinetics affect mean arterial pressure (MAP), heart rate (HR), kidney function, and kidney structure. We found that the administration of all three rHb solutions caused mild hypertension and bradycardia 30 minutes after infusion. However, acute changes in glomerular filtration rate (GFR) were not detected, even though histological analysis was performed 72 hours after treatment revealed some structural changes. All the rHb solutions resulted in hypertension 30 minutes after a 10% topload administration. Regardless of their properties, the presence of acellular Hb causes significant alterations to kidney tissue.

Keywords:

• Blood substitutes
• glomerular filtration rate
• fluorescein-isothiocyanate sinistrin
• acute kidney injury

Acknowledgements

The authors thank Froilan Barra, Cynthia Walser for their preparation of the animal model; Daniel Ortiz for modification of the GFR technique for the animal model; and Frank DeLano for assistance with the histological sample preparation. We also thank John Olson, Jayashree Soman, Eileen Singleton, and particularly Cornelius Varnado for providing the rHb samples. A description of the methods used to produce the samples is given in Varnado et al. [2013] and references therein, and was based on the original work carried out by Somatogen, Inc. (later Baxter Hemoglobin Therapeutics, Inc.). The Olson group has recently discovered that a significant fraction of rHb becomes glycated when expression is made ultra-high in bioreactors by more efficient heme transport and maintenance of high glucose concentrations to increase cell paste yields. These modifications do not appear to affect spectral characteristics or O₂ affinities in phosphate buffers to any great extent but may influence various cellular interactions in vivo.

Disclosure statement

All authors declare no conflicts of interests.