Biomarkers in Renal Transplantation Ischemia Reperfusion Injury

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Ischemia reperfusion injury (IRI) is a choreographed process leading to delayed graft function (DGF) and reduced long-term patency of the transplanted organ. Early identification of recipients of grafts at risk would allow modification of the posttransplant management, and thereby potentially improve short- and long-term outcomes. The recently emerged “omics” technologies together with bioinformatics workup have allowed the integration and analysis of IRI-associated molecular profiles in the context of DGF. Such a systems biological approach promises qualitative information about interdependencies of complex processes such as IRI regulation, rather than offering descriptive tables of differentially regulated features on a transcriptome, proteome, or metabolome level leaking the functional, biological framework. In deceased-donor kidney transplantation as the primary causative factor resulting in IRI and DGF, a distinct signature and choreography of molecular events in the graft before harvesting seems to be associated with subsequent DGF. A systems biological assessment of these molecular changes suggests that processes along inflammation are of pivotal importance for the early stage of IRI. The causal proof of this association has been tested by a double-blinded, randomized, controlled trial of steroid or placebo infusion into deceased donors before the organs were harvested. Thorough systems biological analysis revealed a panel of biomarkers with excellent discrimination. In summary, integrated analysis of omics data has brought forward biomarker candidates and candidate panels that promise early assessment of IRI. However, the clinical utility of these markers still needs to be established in prospective trials in independent patient populations.

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