Normothermic Machine Perfusion Reconstitutes Porcine Kidney Tissue Metabolism But Induces an Inflammatory Response,...

Area of Science:

• Transplantation immunology
• Renal physiology
• Machine perfusion technologies

Background:

• Normothermic machine perfusion (NMP) is a promising strategy to mitigate renal ischemia-reperfusion injury (IRI) after transplantation.
• Optimizing NMP requires understanding its impact on renal metabolism and inflammatory responses.
• The role of the complement system in NMP-induced inflammation remains to be fully elucidated.

Purpose of the Study:

• To assess the effect of complement inhibition on inflammatory responses during NMP of pig kidneys.
• To evaluate renal metabolism using microdialysis during static cold storage (SCS) and NMP.
• To investigate the efficacy of a C5-inhibitor in reducing NMP-associated inflammation.

Main Methods:

• Twenty-two pig kidneys underwent 18 hours of SCS followed by 4 hours of closed-circuit NMP.
• Kidneys were randomized to receive either a C5-inhibitor or a placebo during SCS and NMP.
• Renal metabolism was monitored using microdialysis; inflammatory markers were measured in perfusate and kidney tissue.

Main Results:

• NMP stabilized renal flow, reduced resistance, and promoted urine production.
• Microdialysis showed metabolic recovery during NMP, with metabolites returning to baseline after 4 hours.
• NMP increased inflammatory markers (C3a, sC5b-9, TNF, IL-6, IL-1β, IL-8, IL-10). C5-inhibition significantly reduced perfusate/urine sC5b-9 and tissue IL-1β, but not other markers.

Conclusions:

• Closed-circuit NMP supports renal metabolism but induces significant inflammation, partly complement-dependent.
• C5 inhibition demonstrates a targeted effect on specific complement-mediated inflammatory pathways during NMP.
• Further investigation into broader immune modulation strategies is warranted to optimize NMP for clinical application.