Short, Cool, and Well Oxygenated - HOPE for Kidney Transplantation in a Rodent Model

Abstract

Objectives: The aim of this study was to investigate novel and easily applicable preservation perfusion techniques in kidney grafts obtained from donors after circulatory death (DCD).

Background: A novel perfusion approach, hypothermic oxygenated perfusion (HOPE), used for DCD liver grafts, is based on cold perfusion for 1 hour by an oxygenated solution before implantation. Here, we aimed to test HOPE in a rodent model of kidney grafts associated with substantial warm ischemia.

Methods: Rat kidneys were exposed to 30 minutes in situ warm ischemia, without application of heparin. Kidneys were removed and cold stored for 4 and 18 hours, mimicking DCD organ procurement and conventional preservation. In additional experiments, kidneys were normothermically perfused with oxygenated blood for 1 hour after cold storage. In a third group, kidneys were perfused by HOPE for 1 hour after cold storage. In each group, orthotopic kidney transplantation was performed after recipient nephrectomy.

Results: HOPE-treated DCD kidneys showed dramatically better function after transplantation, than cold-stored grafts in terms of nuclear injury, macrophage activation, endothelium activation, tubulus damage, and graft function. A short period of warm oxygenated perfusion before implantation improved graft quality as compared with cold storage, but was significantly less effective in all endpoints compared with HOPE. The effect of HOPE was dependent on perfusate oxygenation in the cold.

Conclusions: HOPE of DCD kidneys was superior to other clinically used preservation approaches, consistent to earlier results in livers. On the basis of this, we assume a strong and generalized effect on solid organ viability by HOPE before transplantation. These results justify a clinical trial.