Langberg Nina Elisabeth, Jenssen Trond G, Haugen Anders J, Mjøen Geir, Birkeland Kåre I, Åsberg Anders, Hartmann Anders, Dahle Dag Olav
Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
Transplant Direct. 2021 Dec 13;8(1):e1262. doi: 10.1097/TXD.0000000000001262. eCollection 2022 Jan.
Endothelial dysfunction is an early and potentially reversible stage in the atherosclerotic process. We assessed endothelial dysfunction noninvasively in kidney transplant recipients (KTRs) and evaluated the association with mortality and graft outcomes.
Flow-mediated dilation (FMD) was measured in arteria brachialis by ultrasound, with baseline diameters obtained at rest and maximal diameters obtained during reactive hyperemia occurring after 5 min of forearm occlusion. FMD% is the percentage difference of flow-mediated dilation relative to baseline. Endpoints on mortality and graft outcomes were collected from The Norwegian Renal Registry. The distribution of risk according to FMD levels was assessed in Cox regression using a restricted cubic spline function. FMD was dichotomized using receiver operating characteristic analysis to identify optimal cut points at maximal sensitivity and specificity.
From a total of 269 KTRs in 2012, 152 (56.5%) were eligible and examined 10 wk after transplantation, and 145 had successful FMD measurements. During a mean follow-up of 6.5 y, 26 patients died, 11 lost their graft, and 34 experienced either graft loss or death. Mortality increased with lower FMD levels until about 5% dilation and did not change with further reduction in FMD% ( for nonlinearity <0.01). An optimal cut point of FMD ≤5.36% defined impaired endothelial function and FMD% below this level, was associated with fatal outcome, hazard ratio (HR), 9.80 (1.29-74.62), = 0.03, uncensored graft loss, HR, 7.80 (1.83-33.30), = 0.01, but an association with death-censored graft loss was lost after adjusting for pulse pressure, HR, 4.58 (0.55-37.92), = 0.16.
We found that impaired FMD is strongly associated with mortality in KTRs.
内皮功能障碍是动脉粥样硬化进程中的一个早期且可能可逆的阶段。我们对肾移植受者（KTRs）的内皮功能障碍进行了非侵入性评估，并评估了其与死亡率和移植肾结局的相关性。
通过超声测量肱动脉的血流介导的血管舒张功能（FMD），在静息状态下获得基线直径，并在前臂阻断5分钟后反应性充血期间获得最大直径。FMD%是血流介导的血管舒张相对于基线的百分比差异。从挪威肾脏登记处收集死亡率和移植肾结局的终点数据。使用受限立方样条函数在Cox回归中评估根据FMD水平的风险分布。使用受试者工作特征分析将FMD进行二分法，以确定在最大敏感性和特异性时的最佳切点。
在2012年的总共269名KTRs中，152名（56.5%）符合条件并在移植后10周接受检查，145名成功进行了FMD测量。在平均6.5年的随访期间，26名患者死亡，11名失去移植肾，34名经历了移植肾丢失或死亡。死亡率随着FMD水平降低而增加，直到扩张约5%，并且随着FMD%进一步降低而没有变化（非线性<0.01）。FMD≤5.36%的最佳切点定义为内皮功能受损，FMD%低于此水平与致命结局相关，风险比（HR）为9.80（1.29 - 74.62），P = 0.03，未删失的移植肾丢失，HR为7.80（1.83 - 33.30），P = 0.01，但在调整脉压后与死亡删失的移植肾丢失的关联消失，HR为4.58（0.55 - 37.92），P = 0.16。
我们发现FMD受损与KTRs的死亡率密切相关。
