Barriers and Advances in Kidney Preservation

Abstract

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.

Donor anti-complement therapy: Complement-ing the protection array?

“…With the increased use of marginal donors, and the associated fragility of the collected organs, all efforts must be deployed to prevent IRI lesions. While several new strategies exist at the organ level to improve preservation, 5 improving outcome for marginal organs requires a better management of the full peritransplantation window, from the donor, through the organ collection and transport, to the recipient immediately after reperfusion. The solution will likely be multifactorial, combining both technological and pharmacological approaches, and studies such as those conducted by Danobeitia et al 4 demonstrate that anticomplement is an integral part of this strategy (Figure 1).…”

“…Adapted from ref. 5 with permission. EPO, erythropoietin; IRI, ischemia‐reperfusion injury; miRN, micro RNA; PEG, PolyEthylene Glycol; rhC1INH, human recombinant C1 inhibitor…”

A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

“…With oxygenation, temperature is one key parameter in renal graft preservation. Based on cell metabolic reduction, hypothermic storage is the main strategy to minimize ischemic (and/or reperfusive) injuries [3,99]. RCM hemoglobin stabilizes cortical oxygen and slows the ischemic O 2 disappearance; exploratory experiments where parameters and processes were adjusted at their 4 • C-equivalent showed that low temperature stabilizes tissue oxygen.…”

“…RCM hemoglobin stabilizes cortical oxygen and slows the ischemic O 2 disappearance; exploratory experiments where parameters and processes were adjusted at their 4 • C-equivalent showed that low temperature stabilizes tissue oxygen. Thus RCM could also be used as a helping tool to analyze the role of temperature on the one hand, and hemoglobin and various other oxygen carriers, on the other hand [3,99].…”

“…Renal hypoxia is considered a common root of acute and chronic kidney diseases [1,2]. In transplantation, the unavoidable ischemia-reperfusion sequence (IR) is involved in short and long-term graft dysfunctions and injuries (IRI) [3][4][5].…”