Abstract：
OBJECTIVE: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient.
METHODS: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes.
RESULTS: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year.
CONCLUSIONS: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors\' death on long-term graft function.
METHODS: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes.
RESULTS: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year.
CONCLUSIONS: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors\' death on long-term graft function.
摘要：
目的：与活体供者和死于其他原因的人相比，死于中风和相关特征的供者的移植结果更差。我们假设已故的捐赠者，尤其是那些死于中风的人，脑血管性状的多基因负担升高。我们进一步假设，这种供体多基因负担与受体的移植物结局较差有关。
方法：使用来自七个不同欧洲血统移植队列的6666名死者和活体肾脏捐献者的数据集，我们调查了多基因负担对脑血管性状的作用(高血压，中风,和颅内动脉瘤（IA））对供体死亡年龄和受体移植物结局的影响。
结果：我们发现死于中风的肾脏捐献者颅内动脉瘤和高血压多基因风险评分升高，与健康对照和活体捐赠者相比。这种负担与卒中死亡的捐献者的死亡年龄有关。供者多基因高血压风险增加与移植物长期存活率降低(HR:1.44,95%CI[1.07,1.93])和高血压负担增加相关。颅内动脉瘤与1年时受者估计肾小球滤过率(eGFR)降低相关.
结论：总的来说，此处的结果证明了与供者死亡相关的遗传因素对长期移植物功能的影响.
方法：使用来自七个不同欧洲血统移植队列的6666名死者和活体肾脏捐献者的数据集，我们调查了多基因负担对脑血管性状的作用(高血压，中风,和颅内动脉瘤（IA））对供体死亡年龄和受体移植物结局的影响。
结果：我们发现死于中风的肾脏捐献者颅内动脉瘤和高血压多基因风险评分升高，与健康对照和活体捐赠者相比。这种负担与卒中死亡的捐献者的死亡年龄有关。供者多基因高血压风险增加与移植物长期存活率降低(HR:1.44,95%CI[1.07,1.93])和高血压负担增加相关。颅内动脉瘤与1年时受者估计肾小球滤过率(eGFR)降低相关.
结论：总的来说，此处的结果证明了与供者死亡相关的遗传因素对长期移植物功能的影响.
