Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Surgery, NYU Langone Medical Center, New York, New York.
Am J Transplant. 2019 Feb;19(2):585-590. doi: 10.1111/ajt.15174. Epub 2018 Dec 4.
Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.38 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.
延迟移植物功能(DGF)使 20%-40%的死亡供体肾脏移植复杂化,与住院时间延长和随后的移植物失功有关。对特定移植物 DGF 风险的准确预测可以影响器官分配、患者咨询和术后计划。线粒体功能障碍是缺血再灌注损伤中组织健康的报告替代指标,也可能是器官移植后组织健康的替代指标。为了了解线粒体膜电位(MMP)在临床决策中的潜在应用,我们分析了较低的 MMP(衡量线粒体功能障碍的指标)是否与 DGF 有关。在一项前瞻性、单中心概念验证研究中,我们测量了 28 例死亡供体肾脏的移植前 MMP,并分析了 MMP 与 DGF 之间的关系。我们使用混合登记增强回归来调整供体和受体特征,通过利用 Scientific Registry of Transplant Recipients 数据最小化过度拟合。MMP 水平范围为 964-28333 单位。低 MMP 肾脏(MMP<4000)更可能来自女性供体(75%比 10%,P=0.002)和心脏死亡后捐献者(75%比 12%,P=0.004)。MMP 水平每降低 10%,DGF 的可能性就会增加 38%(调整后的优势比=1.38,P=0.01)。总之,MMP 可能是肾脏移植中组织健康的有前途的移植前替代指标,并且在进一步验证后,通过其与 DGF 的独立关联,可以改善临床决策。