Ex-situ evaluation of donor kidneys during isolated machine perfusion

面对供体移植物的日益短缺，使用来自延长标准供体的肾脏已越来越被接受。然而，这些器官的缺血耐受性降低可能对实质器官功能产生负面影响，并损害移植后的恢复。为了突破接受标准的极限，保护外科医生避免过度按压的工具至关重要。因此，已经建立了冷或温灌注的非原位灌注用于移植前的移植物修复。然而，评估措施的披露，有助于决定边缘移植是否最终应该用于移植或宁可被丢弃，是至关重要的，但基本上是不发达的。在临床常规中，预防性丢弃移植物加剧了全球器官短缺，而过度乐观地使用边缘器官可能导致初级功能和生存率降低。在低温机器灌注过程中获得的大量生物标志物已经被提出用于评估移植物的形态学损伤，但与移植肾脏的深层功能的相关性通常不足。在体外机器灌注过程中，通过无创分离光谱测量13C和12C碳同位素来测量柠檬酸循环代谢活性的评估潜力是本提案的主要目的。使用故意制造的“好”、“一般”和“坏”肾脏，13C测试应评估其区分各组的潜力。此外，它的鉴别潜力应与使用更传统的以及一些将在同一实验中确定的新的生物标志物进行比较。因此，本研究旨在验证猪非原位肾机灌注模型的新诊断概念。

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.