Abstract：
OBJECTIVE: To investigate whether ischemia alters donor kidney metabolism and whether these changes are associated with organ function.
BACKGROUND: An unmet need in kidney transplantation is the ability to predict posttransplant organ function before transplantation. Key to such viability testing is a profound understanding of the organ\'s complex biochemistry and how ischemia, inevitable during the transplantation process, influences this.
METHODS: First, metabolic changes in perfusate glucose, lactate, and 20 amino acids, induced by no, 1 hour of warm, or 22 hours of cold ischemia, were investigated during 4-hour perfusion of pig kidneys with autologous whole blood (n = 6/group), simulating the ischemia-reperfusion phase of transplantation. Next, we confirmed similar metabolic changes during normothermic preservation of pigs (n = 3/group; n = 4 for cold ischemia) and discarded human kidneys (n = 6) perfused with a red blood cell-based perfusate.
RESULTS: At 2 hours of perfusion with autologous whole blood, abundances of 17/20 amino acids were significantly different between groups, reflecting the type of ischemia. Amino acid changes at 15 minutes and 2 hours of perfusion correlated with future kidney function during perfusion. Similar metabolic patterns were observed during perfusion preservation of pig and discarded human donor kidneys, suggesting an opportunity to assess kidney viability before transplantation.
CONCLUSIONS: Perfusate metabolite changes during normothermic kidney perfusion represent a unique noninvasive opportunity to assess graft viability. These findings now need validation in transplant studies.
BACKGROUND: An unmet need in kidney transplantation is the ability to predict posttransplant organ function before transplantation. Key to such viability testing is a profound understanding of the organ\'s complex biochemistry and how ischemia, inevitable during the transplantation process, influences this.
METHODS: First, metabolic changes in perfusate glucose, lactate, and 20 amino acids, induced by no, 1 hour of warm, or 22 hours of cold ischemia, were investigated during 4-hour perfusion of pig kidneys with autologous whole blood (n = 6/group), simulating the ischemia-reperfusion phase of transplantation. Next, we confirmed similar metabolic changes during normothermic preservation of pigs (n = 3/group; n = 4 for cold ischemia) and discarded human kidneys (n = 6) perfused with a red blood cell-based perfusate.
RESULTS: At 2 hours of perfusion with autologous whole blood, abundances of 17/20 amino acids were significantly different between groups, reflecting the type of ischemia. Amino acid changes at 15 minutes and 2 hours of perfusion correlated with future kidney function during perfusion. Similar metabolic patterns were observed during perfusion preservation of pig and discarded human donor kidneys, suggesting an opportunity to assess kidney viability before transplantation.
CONCLUSIONS: Perfusate metabolite changes during normothermic kidney perfusion represent a unique noninvasive opportunity to assess graft viability. These findings now need validation in transplant studies.
摘要：
目的：研究缺血是否改变供体肾脏代谢，以及这些改变是否与器官功能相关。
背景：肾移植中未满足的需求是在移植前预测移植后器官功能的能力。这种活力测试的关键是深刻了解器官的复杂生物化学以及缺血，在移植过程中不可避免，影响这一点。
方法：首先，葡萄糖的代谢变化，乳酸和20个氨基酸诱导，1h的温暖，或22h的冷缺血被研究在4h灌注猪肾脏与自体全血（n=6/组），模拟移植的缺血再灌注阶段。接下来,我们证实了正常体温保存猪(n=3/组;冷缺血时n=4)和废弃的人肾(n=6)灌注红细胞灌注液过程中相似的代谢变化.
结果：自体全血灌注2小时后，17/20氨基酸的丰度在组间有显著差异，反映缺血的类型。灌注15分钟和2小时的氨基酸变化与灌注期间未来的肾功能相关。在猪和丢弃的人类供体肾脏的灌注保存过程中观察到类似的代谢模式，提示移植前评估肾脏活力的机会。
结论：常温肾脏灌注过程中灌注酸代谢物的变化代表了评估移植物生存力的独特非侵入性机会。这些发现现在需要在移植研究中得到验证。
背景：肾移植中未满足的需求是在移植前预测移植后器官功能的能力。这种活力测试的关键是深刻了解器官的复杂生物化学以及缺血，在移植过程中不可避免，影响这一点。
方法：首先，葡萄糖的代谢变化，乳酸和20个氨基酸诱导，1h的温暖，或22h的冷缺血被研究在4h灌注猪肾脏与自体全血（n=6/组），模拟移植的缺血再灌注阶段。接下来,我们证实了正常体温保存猪(n=3/组;冷缺血时n=4)和废弃的人肾(n=6)灌注红细胞灌注液过程中相似的代谢变化.
结果：自体全血灌注2小时后，17/20氨基酸的丰度在组间有显著差异，反映缺血的类型。灌注15分钟和2小时的氨基酸变化与灌注期间未来的肾功能相关。在猪和丢弃的人类供体肾脏的灌注保存过程中观察到类似的代谢模式，提示移植前评估肾脏活力的机会。
结论：常温肾脏灌注过程中灌注酸代谢物的变化代表了评估移植物生存力的独特非侵入性机会。这些发现现在需要在移植研究中得到验证。
