Between 2010 and 2013, we recorded 66 cases of failed organ donation after brain death (DBD) due to the excessive use of the vasoactive drugs resulting in impaired hepatic and/or renal function. To investigate the effect of extracorporeal membrane oxygenation (ECMO) in donor management, ECMO was used to provide support for DBD donors with circulatory and/or respiratory failure from 2013 to 2015. A retrospective cohort study between circulatory non-stable DBD with vasoactive drugs (DBD-drug) and circulatory non-stable DBD with ECMO (DBD-ECMO) was designed to compare the transplant outcomes. A total of 19 brain death donors were supported by ECMO. The incidence rate of post-transplant liver primary non-function (PNF) was 10% (two of 20) in DBD-drug group and zero in DBD-ECMO group. Kidney function indicators, including creatinine clearance and urine production, were significantly better in DBD-ECMO group, as well as the kidney delayed graft function (DGF) rate was found to be decreased by the use of ECMO in our study. Donation success rate increased steadily from 47.8% in 2011 to 84.6% in 2014 after the ECMO intervention. The use of ECMO in assisting circulatory and respiratory function of DBD can reduce liver and kidney injury from vasoactive drugs, thereby improving organ quality and reducing the organ discard rates.

There is an urgent need to improve the quality of donor organs obtained after cardiac death. In the present study, we examined the potential mechanisms through which A20 protects renal cells against ischemia/reperfusion injury (IRI) following either hypothermic machine perfusion (HMP) or static cold storage (CS) of the kidneys in a rabbit model. The expression of markers of apoptosis, necroptosis and inflammation in frozen kidney tissues were detected by western blot analysis, RT-qPCR and ELISA. Compared with the CS group, A20 expression was significantly higher in the tissue from the HMP group (P<0.01). By contrast, the expression of nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) was significantly lower in HMP group (P<0.01), whereas IκBα expression was significantly higher (P<0.01). The expression of apoptosis signal-regulating kinase 1 (ASK1), phosphorylated (p-)c-Jun N-terminal kinase (JNK) and activated caspase-3 in the HMP group was significantly downregulated compared with that in the CS group (all P<0.01). In addition, A20 inhibited receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis in the kidney. RIPK3 expression in the HMP group was significantly lower than that in the CS group (P<0.01), although the levels in both groups were higher than those in the sham group (P<0.01). Based on these findings, we propose a novel mechanism underlying the anti-apoptotic effect of A20 in renal cells in which A20 binds to ASK1 and promotes the degradation of ASK1 leading to the suppression of JNK activation and eventually, to the blockade of apoptosis. Thus, HMP reduces inflammation, apoptosis and necroptosis by upregulating the expression of A20; this mechanism may be responsible for protecting the kidney against IRI.

Oxidative stress induced by ischemia and hypoxia in the livers of donors after brain death (DBD) is associated with poor organ function and low patient survival rates in those receiving DBD liver transplants. Peroxiredoxin 6 (Prdx6) can defend cells against liver damage induced by oxidative stress. The present study aimed to investigate the role of Prdx6 in ischemia- and hypoxia-induced liver damage in DBD livers. Liver tissue samples from ten DBD patients were collected. The control group constituted of six liver samples from patients with liver hemangioma that had accepted tumor excision surgery. Protein expression levels were determined by western blotting, cell viability was assessed using a CCK-8 assay, intracellular reactive oxygen species (ROS) levels were measured using a ROS assay kit, and phospholipase A2 (PLA2) activity was measured using a PLA2 assay kit. In DBD liver samples, Prdx6 expression was downregulated and the nuclear factor-κB (NF-κB) signaling pathway was activated. Furthermore, when human liver L02 cells were exposed to ischemia and hypoxia, the expression of Prdx6 was reduced, causing an increase in reactive oxygen species (ROS); this in turn activated NF-κB signaling and lowered cell viability (P<0.01). In agreement, overexpression of Prdx6 reduced ROS levels and improved cell viability. It was also demonstrated that inhibition of NF-κB increased Prdx6 expression, while inhibition of Prdx6 limited PLA2 activity, exacerbating ischemia- and hypoxia-induced cell damage. This data suggests that Prdx6 and its PLA2 activity have a protective role in DBD livers, the expression of which is regulated by NF-κB. Thus, Prdx6 may be a novel target to alleviate liver damage in DBD.

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