Reduction of Renal Preservation/Reperfusion Injury by Controlled Hyperthermia During Ex Vivo Machine Perfusion

Abstract

The possible reno-protective effect of a controlled brief heat-shock treatment during isolated ex vivo machine perfusion of donor grafts prior to reperfusion should be investigated in a primary in vitro study. Porcine kidneys (n = 14) were retrieved after 20 minutes of cardiac standstill of the donor and subjected to 20 hours of static cold storage in University of Wisconsin solution. Prior to reperfusion, kidneys were subjected to 2 hours of reconditioning machine perfusion with gradual increase in perfusion temperature up to 35°C. In half of the kidneys (n = 7), a brief hyperthermic impulse (10 minutes perfusion at 42°C) was implemented in the machine perfusion period. Functional recovery of the grafts was observed upon normothermic reperfusion in vitro. Hyperthermic treatment resulted in a 50% increase of heat shock protein (HSP) 70 and HSP 27 mRNA and was accompanied by ~ 50% improvement of tubular re-absorption of sodium and glucose upon reperfusion, compared with the controls. Furthermore, renal loss of aspartate aminotransferase was significantly reduced to one-third of the controls as was urinary protein loss, evaluated by the albumin to creatinine ratio. It is concluded that ex vivo heat-shock treatment seems to be an easily implementable and promising option to enhance renal self-defense machinery against reperfusion injury after preservation that merits further investigation in preclinical models. Clinical kidney transplantation more and more relies on the use of extended criteria donor organs that have been predamaged prior to retrieval or are likely less than optimal quality. Along with the increasing proportion of those organs that bear an enhanced susceptibility to injurious triggers upon ischemic preservation, 1,2 tissue alterations

Single-Cell Heterogeneity Restorative Chimeric Engineering Nanoparticles for Alleviating Antibody-Mediated Allograft Injury

“…The porcine kidney transplantation model has been widely used as a tool for clinical translational research . Renal perfusion is the basis for oxygen and nutrient transport, and quantitative assessment of transplanted kidney perfusion helps clinicians recognize the pathophysiological changes in the transplanted kidney . As shown in Figure A, to evaluate the effect of applying DSA trappers, an allogeneic porcine kidney transplantation model was successfully established, and the transplanted kidney perfusion was verified by multitemporal CT angiography.…”

Perfusate Composition and Duration of Ex-Vivo Normothermic Perfusion in Kidney Transplantation: A Systematic Review

“…Heat-shock proteins are well known as a defense mechanism induced by stressful stimuli such as hypoxia or hyperthemia ( 41 , 42 ). Minor et al demonstrated that with gradual rewarming (or “controlled hyperthermia”), they found a 50% increase of heat-shock proteins, which correlated to improvement of tubular reabsorption of sodium and glucose upon reperfusion, and reduced loss of urinary protein compared with controls, meriting further exploration of this technique in preclinical models ( 43 ). As a result of this work, there is emerging evidence that avoiding the abrupt temperature changes may be protective against IRI.…”

Normothermic machine perfusion of kidneys: current strategies and future perspectives

“…Another group propagated a short period of hyperthermic perfusion (10 min at 42°C) of porcine kidneys (20 h SCS; 2 h perfusion with gradual increase of temperature to 35°C), as this led to a 50% increase of heat shock proteins, potentially inducing repair mechanism and tolerance against subsequent cellular injury [59].…”

“…As the Cytosorb adsorber is not cytokine specific and might even eliminate important anti-inflammatory mediators, the group further explored the use of a hemoadsorber to selectively remove pro-inflammatory cytokines. The use of a hemoadsorber resulted in a reduced expression of DGF-associated genes [58 Another group propagated a short period of hyperthermic perfusion (10 min at 428C) of porcine kidneys (20 h SCS; 2 h perfusion with gradual increase of temperature to 358C), as this led to a 50% increase of heat shock proteins, potentially inducing repair mechanism and tolerance against subsequent cellular injury [59].…”