In order to enlarge the amount of kidneys available for transplantation new strategies must be developed. At present, the quality of kidneys donated after cardiac death (DCD) is insufficient for transplantation (e.g. non or delayed graft function) if stored conventionally on ice¹. As artificial oxygen carriers have already been used successfully for organ preservation², the strategy of using albumin-derived, perfluorodecalin-based artificial oxygen carriers (APOCs) in an ex vivo normothermic maschine perfusion is a promising approach to regenerate ischemic DCD kidneys.

To identify the improvement of APOCs on organ quality, rat DCD kidneys (120 min of ischemia) were perfused pressure-controlled (60-80mmHg) for 2 hours with Krebs-Henseleit-buffer (KH)/ bovine serum albumin (BSA) with or without presence of APOCs, respectively (Perfusion KH+BSA+APOCs or Perfusion KH+BSA). Perfusion-free controls evaluated after 0min (-control) and 120min of ischemia (+control) were investigated. The oxygen consumption before and behind the kidneys were monitored in the perfusate with clark electrodes. Other read-out parameters were kidney´s brush border damage detected with periodic acid-Schiff (PAS) staining, TNFα-receptor-expression and the evaluation of apoptosis using the TUNEL method.

Kidneys perfused with APOCs showed a higher oxygen consumption (0.014 mlO₂/g kidney) with regard to control kidneys (0.010 mlO₂/g kidney). Furthermore, PAS staining revealed that perfusion with APOCs improved slightly but significantly the regeneration of the tubular brush border compared to perfusion with KH+BSA. However, the TUNEL method and the TNFα-receptor staining failed in demonstrating any improvements concerning the cell survival or receptor expression. Compared to the non-perfused +control kidneys, the PAS and TUNEL staining illustrated that perfusion did not increase either cell damage or cell survival. Remarkably, TNFα-receptor-expression was even reduced after perfusion.

In conclusion, normothermic perfusion was well tolerated by the DCD kidneys and helped to maintain the kidney´s quality after 120 min of ischemia for 2 hours. Some parameters such as intactness of the tubular brush border and oxygen consumption were actually improved by the action of APOCs.

 

References:

1. Hosgood, S. A.,Nicholson, M. L. (2011). Normothermic kidney preservation. Curr Opin Organ Transplant 16, 169-173.

2. Ferenz, K.B., Steinbicker A.U. (2019). Artificial Oxygen Carriers-Past, Present and Future- a Review of the Most Innovative and Clinically Relevant Concepts J Pharmacol Exp Ther 369:300-310