Ex-situ evaluation of donor kidneys during isolated machine perfusion

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In face of the increasing shortage of donor grafts the use of kidneys from extended criteria donors has become increasingly accepted. The reduced ischemic tolerance of these organs, however, may have a negative impact on parenchymal organ function and compromise recovery after transplantation.In line with the attempt to push the limits of acceptance criteria, tools to safeguard the surgeon from over-pushing are of crucial importance. Thus, ex situ perfusion with cold or warm perfusates has been established for graft reconditioning prior to transplantation. However, the disclosure of evaluative measures, helping to decide whether a marginal graft should eventually be used for transplantation or rather be discarded are of utmost importance but yet basically underdeveloped.In clinical routine, precautious discard of grafts intensifies global organ shortage, while over-optimistic use of marginal organs may result in reduced primary function and survival rates. A plethora of biomarkers, obtained during hypothermic machine perfusion, has already been proposed to evaluate morphological injury to the graft but correlations with ulterior function of transplanted kidneys were generally insufficient. It is the main aim of the present proposal to scrutinize the evaluative potential of measuring the metabolic activity of the citrate cycle by non-invasive separated spectroscopic measurement of 13C and 12C carbon isotopes during ex vivo machine perfusion.Using deliberately created ‘good’, ’fair’ and ‘bad’ kidneys, the 13C test shall be evaluated for its potential to discriminate between the groups. Moreover, its discriminative potential shall be compared to the use of more conventional as well as some novel biomarkers that will be determined during the same experiments. The present research is thus intended to validate a new diagnostic concept in an ex situ renal machine perfusion model in pigs.