First-in-man controlled rewarming and normothermic perfusion with cell-free solution of a kidney prior to transplantation

Abstract

Cold preservation sensitizes organ grafts to exacerbation of tissue injury upon reperfusion. This reperfusion injury is not fully explained by the mere re‐introduction of oxygen but rather is pertinent to the immediate rise in metabolic turnover associated with the abrupt restoration of normothermia. Here we report the first clinical case of gradual resumption of graft temperature upon ex vivo machine perfusion from hypothermia up to normothermic conditions using cell‐free buffer as a perfusate. A kidney graft from an extended criteria donor was put on the machine after 12.5 hours of cold storage. During ex vivo perfusion, perfusion pressure and temperature were gradually elevated from 30 mm Hg and 8°C to 75 mm Hg and 35°C, respectively. Perfusate consisted of diluted Steen solution, oxygenated with 100% oxygen. Final flow rates at 35°C were 850 mL/min. The kidney was transplanted without complications and showed good immediate function. Serum creatinine fell from preoperative 720 µmol/L to 506 µmol/L during the first 24 hours after transplantation. Clearance after 1 week was 43.1 mL/min. Controlled oxygenated rewarming prior to transplantation can be performed up to normothermia without blood components or artificial oxygen carriers and may represent a promising tool to mitigate cold‐induced reperfusion injury or to evaluate graft performance.

Treatment of transplant kidneys during machine perfusion

“…It is a new technology that requires significant resources and at present there is no consensus on the optimal strategy. The optimal time, pressure, flow, temperature, partial pressure of oxygen, sequence with cold static storage and perfusion solutions are all still under investigation [45]. Furthermore, the clinical application of NMP in kidney transplantation is sparse, with only a handful of single case reports [45,46] and one case series [11].…”

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

“…A controversy still exists if machine perfusion ought to be done up-front, immediately after graft procurement 27 despite of incurring logistic inconveniences, or if a brief, end-ischemic perfusion period after transport of the organ by static cold storage would be sufficient and more easily implementable in clinical routine. 28,29 Ex vivo conditioning of the graft by CH would be possible in either modality.…”

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

“…COR reduces ROS production, improves mitochondrial and aerobic efficiency, enhances kidney function compared to NMP, and improves post-transplant graft outcome compared to CS [31]. As clinical feasibility is demonstrated [32], COR appears to be an alternative post CS compared to NMP [29,33].…”