Donor genetic burden for cerebrovascular risk and kidney transplant outcome

• DOI: 10.1007/s40620-024-01973-0
• Publication Date: 2024-05-29T15:02:25Z
• Authors: Kane E. Collins; Edmund Gilbert; Vincent Mauduit; Katherine A. Benson; Elhussein A. E. E...; Conall O’Seaghdha; Claire Hill; Amy Jayne McKnight; Alexander P. Maxwell; Peter J. van der ...; Martin H. de Borst; Weihua Guan; Pamala A. Jacobson; Ajay K. Israni; Brendan J. Keating; Graham M. Lord; Salla Markkinen; Ilkka Helanterä; Kati Hyvärinen; Jukka Partanen; Stephen F. Madden; Sophie Limou; Gianpiero L. Cava...; Peter J. Conlon
• Keywords: Male; Adult; 0301 basic medicine; Multifactorial Inheritance; Time Factors; [SDV]Life Sciences [q-bio]; Donors; Surgery, anesthesiology, intensive care, radiology; 610; Risk Assessment; 03 medical and health sciences; Risk Factors; Genetics; Living Donors; Humans; Genetic Predisposition to Disease; Graft Survival; Age Factors; 600; Intracranial Aneurysm; Middle Aged; Kidney Transplantation; Tissue Donors; [SDV] Life Sciences [q-bio]; Stroke; Polygenic risk scores; Treatment Outcome; Hypertension; Post-transplant eGFR; Original Article; Female; Glomerular Filtration Rate

Abstract 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.

Graphical Abstract