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Donor genetic burden for cerebrovascular risk and kidney transplant outcome
Kane E Collins1,2,3, Edmund Gilbert1,2, Vincent Mauduit4
1School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Insights
Deceased kidney donors with a genetic predisposition for stroke-related conditions, such as hypertension and intracranial aneurysm, are linked to poorer transplant outcomes. This highlights the impact of donor genetics on long-term kidney graft survival.
Area of Science:
- Genetics
- Nephrology
- Transplantation
Background:
- Kidney grafts from donors who died of stroke have worse outcomes than those from living donors or donors who died of other causes.
- A hypothesis suggests deceased donors, especially stroke victims, carry a higher polygenic burden for cerebrovascular traits, impacting graft outcomes.
Purpose of the Study:
- To investigate the association between polygenic burden for cerebrovascular traits in deceased kidney donors and recipient graft outcomes.
- To determine if donor polygenic risk scores for hypertension, stroke, and intracranial aneurysm correlate with donor age of death and graft survival.
Main Methods:
- Utilized a dataset of 6,666 deceased and living kidney donors from seven European ancestry transplant cohorts.
- Examined polygenic burden for hypertension, stroke, and intracranial aneurysm in relation to donor death cause and recipient graft outcomes.
Main Results:
- Donors who died of stroke exhibited elevated polygenic risk scores for intracranial aneurysm and hypertension compared to controls.
- Increased donor polygenic risk for hypertension correlated with reduced long-term graft survival (HR: 1.44).
- Higher donor polygenic burden for hypertension and intracranial aneurysm was associated with reduced 1-year recipient estimated glomerular filtration rate (eGFR).
Conclusions:
- Inherited genetic factors in deceased donors significantly influence long-term kidney graft function.
- Polygenic risk scores for cerebrovascular traits in donors may serve as predictive markers for transplant success.
Background And Hypothesis:
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.
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