Donor genetic burden for cerebrovascular risk and kidney transplant outcome.
Donors
Genetics
Polygenic risk scores
Post-transplant eGFR
Stroke
Journal
Journal of nephrology
ISSN: 1724-6059
Titre abrégé: J Nephrol
Pays: Italy
ID NLM: 9012268
Informations de publication
Date de publication:
29 May 2024
29 May 2024
Historique:
received:
20
12
2023
accepted:
26
04
2024
medline:
29
5
2024
pubmed:
29
5
2024
entrez:
29
5
2024
Statut:
aheadofprint
Résumé
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. 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. 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. Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function.
Sections du résumé
BACKGROUND AND HYPOTHESIS
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
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
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
CONCLUSIONS
Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function.
Identifiants
pubmed: 38809363
doi: 10.1007/s40620-024-01973-0
pii: 10.1007/s40620-024-01973-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Science Foundation Ireland
ID : 18/CRT/6214
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 15/IA/3152
Pays : Ireland
Organisme : Wellcome Trust
ID : 076113
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 090355/A/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 090355/B/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 088849/Z/09/Z
Pays : United Kingdom
Organisme : Pays de la Loire region
ID : 2018-09998
Organisme : UK Research and Innovation
ID : MC_PC_20026
Organisme : Medical Research Council
ID : G0600698
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J006742/1; G0802068
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K002996/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801537/ID: 88245
Pays : United Kingdom
Organisme : Guy's & St Thomas' Foundation
ID : R080530
Organisme : Guy's & St Thomas' Foundation
ID : R090782
Organisme : Seventh Framework Programme
ID : HEALTHF5-2010-260687
Organisme : Atlantic Philanthropies
ID : ES/L008459/1
Informations de copyright
© 2024. The Author(s).
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