Normothermic kidney perfusion: An overview of protocols and strategies

Abstract

Normothermic machine perfusion (NMP) technologies are emerging as an important adjunct in organ preservation and transplantation. NMP can enable the reduction or avoidance of cold ischemia and allows for pretransplant measurement of function and metabolic status to assess the suitability of the organ for transplantation. The key requirement of NMP is to provide an environment that is protective to the organ, ensures optimal oxygen delivery and supports metabolic function. Red blood cell‐based solutions, artificial hemoglobin solutions, and acellular solutions have all been utilized in NMP. However, there is no clear consensus on perfusion protocols. A period of NMP after hypothermic preservation is the most commonly used strategy. As an alternative, several groups have developed and tested the feasibility of more prolonged periods of NMP. There are only a few reports of the application of NMP in clinical kidney transplantation and each uses different approach and conditions. This review details the rationale for NMP protocols considering duration of NMP and different perfusate compositions in experimental and clinical models. We also include a discussion on the mechanistic action of NMP, comparison of subnormothermic and hypothermic conditions, the different logistical approaches and future requirements.

Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion

“…Additionally, we used Hemopure for reperfusion to establish a completely blood-free platform for evaluating targeted therapies. While no standard perfusate composition or perfusion protocol exists, the supplements added to the Hemopure/PlasmaLyte mixture in this study align with those used in previous studies reviewed by Elliot et al [29].…”

Metabolic needs of the kidney graft undergoing normothermic machine perfusion

“…Longer perfusions that aim at repair and rejuvenation come with the additional need for anabolic factors such as essential amino-acids and vitamins. Current protocols are all based on continuous perfusion with red blood cells or an alternate oxygen carrier, an isotonic or/and colloid solution such as albumin, and glucose and amino acids (2)(3)(4)(5)(10)(11)(12)(13) as energy source (14). A detailed overview of the published protocols (including the perfusate composition) is provided in TABLE 1.…”

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

“…The Hosgood et al protocol provides a more physiological environment, with multiple metabolic substrates and red cells as an oxygen carrier. This contrasts with the Minor protocol, which utilises an acellular perfusate based on Steen solution [29,50].…”

“…NMP may utilise red cells as oxygen carriers [50]; however, with the potential for haemolysis to occur, alternatives are desirable.…”