Effects of warm ischaemia combined with cold preservation on the hypoxia-inducible factor 1α pathway in an experimental renal autotransplantation model

Abstract

The HIF-1α pathway appears to be abolished early in response to severe ischaemia. A high degree of ischaemic injury also results in chronic activation of the HIF-1α pathway, diverting it away from the beneficial activation of angiogenesis. Further studies on the finely tuned balance of signals in this pathway may provide diagnostic biomarkers that can determine organ quality during kidney transplantation. Surgical relevance The increased use of marginal donors has highlighted the importance of organ quality in transplantation. Renal ischaemia-reperfusion injury following transplantation induces graft dysfunction. In a porcine model of renal autotransplantation, the induction of regenerative processes, in response to graded degrees of ischaemia, was studied in the post-transplantation phase. There was early abrogation of the hypoxia-inducible factor (HIF) 1α pathway in response to severe ischaemia. High degrees of ischaemic injury induced chronic activation of the HIF-1α pathway, diverting it from the beneficial activation of angiogenesis. Identification of the mechanisms involved in renal regeneration, such as those related to the HIF-1α pathway, are important as these mechanisms can be used to identify novel therapeutic targets or develop diagnostic biomarkers to determine organ quality early in the transplantation process.

Efficacy of the natural oxygen transporter HEMO 2 life ® in cold preservation in a preclinical porcine model of donation after cardiac death

“…While VEGF increase is a priori expected to be beneficial in terms of the vascular network, no correlation emerged between VEGF and function, suggesting that either this increase was not sufficient to bestow organ protection or that this mechanism was hampered during CS. This is concordant with previous results from our group showing the detrimental effect of combined WI and CS on HIF pathway regulation .…”

“…Surgical and kidney procurement have been described in detail . Briefly, after general anesthesia, orotracheal intubation was performed for mechanical ventilation in volume‐controlled mode.…”

Normothermic <em>Ex Vivo</em> Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

“…Currently, organ preservation is based on static cold storage or hypothermic machine perfusion. As a prolonged cold ischemic time has a significant impact on the outcome of kidney function of standard criteria 15 and marginal grafts 8,9 , new preservation techniques minimizing cold storage are of particular interest [16][17][18][19] .…”

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

“…The porcine model of autotransplantation has previously been used to investigate new preservation techniques 14,18,29 . However, the reported postoperative serum creatinine and BUN values of autotransplanted pigs in a heart-beating scenario vary considerably depending on the experimental system 22,30 .…”

“…In addition, porcine and human kidneys demonstrate similarities in the pathophysiology of ischemia reperfusion injury (IRI), biochemistry, and immunological parameters 14 . Thus, porcine renal transplantation is well-suited to investigate new organ preservation methods for marginal kidney grafts [15][16][17] , model human IRI 18 , study immunological pathways and allograft tolerance 19 , provide surgical training [20][21][22] , test new pharmacological therapies 23 , implement new medical devices, and study new immunological mechanisms in xenotransplantation [24][25][26] .…”