Department of Renal Medicine, Sir Charles Gairdner Hospital, Western Australia, Australia.
School of Medicine, University of Western Australia, Perth, Australia.
Transplantation. 2019 Feb;103(2):412-419. doi: 10.1097/TP.0000000000002275.
Prolonged duration of delayed graft function (DGF) may be associated with adverse allograft outcomes, but the association between threshold duration of DGF, acute rejection and long-term allograft loss remains undefined. We aimed to determine the impact of DGF duration on allograft outcomes and to assess whether this association was mediated by acute rejection.
Using data from the Australian and New Zealand Dialysis and Transplant Registry, Cox proportional modeling was used to determine the association between quartiles of DGF duration, acute rejection at 6 months and death-censored graft loss (DCGL). Mediation analysis was conducted to determine whether acute rejection was a causal intermediate between DGF and DCGL.
Of 7668 deceased donor kidney transplants between 1997 and 2014, 1497 (19.5%) recipients experienced DGF requiring dialysis. The median (interquartile range) duration of DGF was 7 (9) days, with 25% requiring dialysis for 14 days or longer. Among recipients who had experienced a DGF duration of 1 to 4 days, the adjusted hazard ratio for duration of 5 to 7, 8 to 13, and 14 days or longer were 1.13 (95% confidence interval [CI], 0.83-1.55; P = 0.43), 1.44 (95% CI, 1.08-1.91; P = 0.013), and 1.99 (95% CI, 1.50-2.65; P < 0.001), respectively, for acute rejection; and were 1.10 (95% CI< 0.73-1.67; P = 0.64), 1.45 (95% CI, 1.00-2.11; P = 0.05) and 1.60 (95% CI, 1.10-2.31; P = 0.01), respectively, for DCGL. On average, 8% of the effects between DGF duration and DCGL were explained by acute rejection.
There was a direct dose-dependent effect between DGF duration and DCGL, with acute rejection explaining less than 10% of the effects between DGF duration and DCGL. Future research identifying other potential modifiable mediators that lies in the causal pathway between DGF duration and allograft loss is essential.
延迟移植物功能（DGF）时间延长可能与移植物不良结局相关，但 DGF 时间阈值、急性排斥反应与长期移植物丢失之间的关系尚未明确。本研究旨在明确 DGF 时间对移植物结局的影响，并评估这种关联是否由急性排斥反应介导。
利用澳大利亚和新西兰透析和移植登记处的数据，采用 Cox 比例风险模型确定 DGF 时间四分位间距、6 个月时急性排斥反应与死亡风险校正移植物丢失（DCGL）之间的关联。采用中介分析确定急性排斥反应是否是 DGF 与 DCGL 之间的因果中介。
在 1997 年至 2014 年间的 7668 例尸肾移植受者中，有 1497 例（19.5%）受者发生 DGF 需行透析治疗。DGF 的中位（四分位间距）持续时间为 7（9）天，25%的受者透析时间为 14 天或更长。在经历 1-4 天 DGF 持续时间的受者中，DGF 持续时间为 5-7 天、8-13 天和 14 天或更长时间者发生急性排斥反应的调整风险比分别为 1.13（95%CI，0.83-1.55；P=0.43）、1.44（95%CI，1.08-1.91；P=0.013）和 1.99（95%CI，1.50-2.65；P＜0.001），而发生 DCGL 的调整风险比分别为 1.10（95%CI＜0.73-1.67；P=0.64）、1.45（95%CI，1.00-2.11；P=0.05）和 1.60（95%CI，1.10-2.31；P=0.01）。平均而言，DGF 持续时间与 DCGL 之间有 8%的影响可由急性排斥反应解释。
DGF 持续时间与 DCGL 之间存在直接的剂量依赖性关系，而急性排斥反应仅能解释 DGF 持续时间与 DCGL 之间 10%以下的关系。确定 DGF 持续时间与移植物丢失之间因果关系途径中的其他潜在可调节中介因素的未来研究至关重要。
