Abstract Background Mitochondrial dysfunction and ischaemia-reperfusion injury correlate with poorer post transplant outcomes in kidney transplantation (Lo Faro, 2024). The COPE COMPARE trial showed that hypothermic oxygenated machine perfusion (HMPO2) of kidneys donated after circulatory death is safe, and improves graft survival compared to non-oxygenated hypothermic machine perfusion (HMP) (Jochmans, 2020). In this study we hypothesised this may be modulated by enhanced mitochondrial protection. We analysed perfusate cardiolipin, a mitochondrial damage-associated molecular pattern, to investigate whether HMPO2 reduces cardiolipin release and impacts post-transplant outcomes. Methods Perfusate samples from COMPARE (ISRCTN32967929) collected at the beginning (P1) and end (P3) of perfusion were selected from paired kidneys (that is one kidney received HMP and the other HMPO2), n = 20 donors. Fluorimetric analysis measured cardiolipin concentrations. Clinical outcomes including creatinine clearance, eGFR, and graft failure were noted at 3, 6 and 12-months. Results End-perfusion cardiolipin was significantly lower in the HMPO2 group (P = 0.049, n = 9) compared to HMP (n = 13) and concentrations significantly correlated with perfusion length. Higher overall cardiolipin correlated with lower 12-month eGFR (P = 0.039) but did not relate to serum creatinine levels or creatinine clearance at 3, 6 or 12-months. Finally, failed grafts (n = 3) associated with higher end-perfusion cardiolipin levels than functioning grafts at 12-months (n = 17, P = 0.006). Conclusions We show high end-perfusion cardiolipin concentrations impact certain clinical outcomes, particularly reduced eGFR, and increased rates of graft failure at 12-months. Lower cardiolipin concentrations in HMPO2 supports the benefit of using HMPO2 for kidney preservation and presents mitoDAMPs as a marker for assessing post-transplant organ injury.
Hobbs et al. (Sun,) studied this question.