The efficacy of HBOC‐201 in ex situ gradual rewarming kidney perfusion in a rat model

Abstract

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin‐based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post‐transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.

Therapeutic Potential of Hemoglobin Derived from the Marine Worm Arenicola marina (M101): A Literature Review of a Breakthrough Innovation

“…Interestingly, Hemopure (HBOC-201) has been approved by the South African drug council for the treatment of anemia. Moreover, this product is allowed to be used in United States in qualified patients to treat severe life-threatening anemia under the FDA’s expanded compassionate use access program [ 20 , 26 , 27 , 28 , 29 ]. Additionally, one randomized, multicenter trial investigation of HBOC-201 in non-cardiac surgery patients indicated that its use reduced RBC transfusions in 43% of patients without notable differences in mortality and serious adverse events, though there was a notable increase in the associated non-serious events (i.e., hypertension and fever) [ 26 ].…”

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

“…HBOC-201 has been evaluated in ex vivo perfused porcine kidney, and demonstrated similar renal function and equivalent tissue oxygen saturation compared to a blood-treated kidney [16]. This molecule has also been evaluated in gradual rewarming protocols (see below), where it demonstrated the ability to withstand a wide range of temperatures [17].…”

Machine preservation of extremities

“…Probably because of early disappointing results with perfluorocarbons, there has been no attempt to use these in extremity perfusion studies. However, HBOCs with the ability to function in a wide range of temperatures, from hypothermic to normothermic, seem to be an option for ex vivo perfusion . Hemoglobin‐based oxygen carrier 201 (HBOC‐201) is an ultra‐purified bovine hemoglobin derivative polymerized with glutaraldehyde; its low P 50 results in lower O 2 affinity than native hemoglobin .…”

“…However, HBOCs with the ability to function in a wide range of temperatures, from hypothermic to normothermic, seem to be an option for ex vivo perfusion. 40 Hemoglobin-based oxygen carrier 201 (HBOC-201) is an ultra-purified bovine hemoglobin derivative polymerized with glutaraldehyde; its low P 50 results in lower O 2 affinity than native hemoglobin. 41 In 2016, Schweizer et al 42 used an HBOC during subnormothermic MP (21°C) for a 14-hour flap perfusion before heterotopic transplantation.…”