Meertens Pommelien, Mellati Azita, Dumbill Richard, Lo Faro M Letizia, Rozenberg Kaithlyn, Mulvey John, Fliri Hans, Ploeg Rutger, Hunter James
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms.
Leiden University Medical Centre, Leiden University, Leiden, Netherlands.
Front Transplant. 2023 May 11;2:1166661. doi: 10.3389/frtra.2023.1166661. eCollection 2023.
Currently there is an urgent need to translate interventions that may be beneficial to marginal donor kidneys prior to transplant, to improve their quality from bench to bedside. This project investigated the effects of CC-4066, a potent dual inhibitor of cyclophilin proteins A and D, treatment during static cold storage (SCS) in a porcine model of renal ischemia-reperfusion injury (IRI) using Normothermic Reperfusion (NR).
Porcine kidneys and autologous blood were retrieved in pairs from a local abattoir ( = 7). One kidney from each pair was randomly allocated to treatment and one allocated to control and flushed with preservation solution containing CC-4066 or vehicle. After 7 h of SCS kidneys underwent 3 h Normothermic Reperfusion (NR) with autologous whole blood while perfusion characteristics and samples were collected.
Perfusion and metabolic parameters showed similar trends and no statistical differences were observed between the groups. IL-6 showed a significant increase over time but no significant difference between groups (-value 0.009 and 0.14 respectively, two-way ANOVA). Oxygen consumption and lactate levels were similar between groups but there was increased vacuolation on histology in the control group.
The addition of CC-4066 during SCS of kidneys is safe and feasible and has no adverse or detrimental effects on perfusion during assessment on NR. There was no difference in cytokine levels although there was a trend towards less vacuolation on histology in the treatment group.
目前迫切需要将可能对边缘供肾在移植前有益的干预措施进行转化，以提高其从实验台到临床的质量。本项目研究了亲环蛋白A和D的强效双重抑制剂CC - 4066在静态冷藏（SCS）期间对猪肾缺血再灌注损伤（IRI）模型采用常温再灌注（NR）治疗的效果。
从当地屠宰场成对获取猪肾和自体血（n = 7）。每对中的一个肾随机分配至治疗组，另一个分配至对照组，并用含CC - 4066或赋形剂的保存液冲洗。在进行7小时的SCS后，肾脏用自体全血进行3小时的常温再灌注（NR），同时收集灌注特征和样本。
灌注和代谢参数呈现相似趋势，两组间未观察到统计学差异。IL - 6随时间显著增加，但组间无显著差异（分别为p值0.009和0.14，双向方差分析）。两组间氧消耗和乳酸水平相似，但对照组组织学上的空泡化增加。
在肾脏SCS期间添加CC - 4066是安全可行的，并且在NR评估期间对灌注没有不良或有害影响。细胞因子水平无差异，尽管治疗组在组织学上空泡化有减少的趋势。
