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. 2025 Mar 4:38:14171.
doi: 10.3389/ti.2025.14171. eCollection 2025.

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Kane E Collins  1   2   3 , Edmund Gilbert  1   2 , Vincent Mauduit  4 , Katherine A Benson  1   2 , Elhussein A E Elhassan  5   6 , Conall O'Seaghdha  5   6 , Claire Hill  7 , Amy Jayne McKnight  7 , Alexander P Maxwell  7 , Peter J van der Most  8 , Martin H de Borst  9 , Weihua Guan  10 , Pamala A Jacobson  11 , Ajay K Israni  12 , Brendan J Keating  13 , Graham M Lord  14 , Salla Markkinen  15 , Ilkka Helanterä  16 , Kati Hyvärinen  15 , Jukka Partanen  15 , Stephen F Madden  17 , Matthew B Lanktree  18 , Sophie Limou  4 , Gianpiero L Cavalleri #  1   2   3 , Peter J Conlon #  5   6
Affiliations

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Kane E Collins et al. Transpl Int. .

Abstract

Kidney transplant outcomes are influenced by donor and recipient age, sex, HLA mismatch, donor type, anti-rejection medication adherence and disease recurrence, but variability in transplant outcomes remains unexplained. We hypothesise that donor and recipient polygenic burden for traits related to kidney function may also influence graft function. We assembled a cohort of 6,060 living and deceased kidney donor-recipient pairs. We calculated polygenic risk scores (PRSs) for kidney function-related traits in both donors and recipients. We investigated the association between these PRSs and recipient eGFR at 1- and 5-year post-transplant as well as graft failure. Donor: hypertension PRS (P < 0.001), eGFR PRS (P < 0.001), and intracranial aneurysm PRS (P = 0.01), along with recipient eGFR PRS (P = 0.001) were associated with eGFR at 1-year post-transplantation. Clinical factors explained 25% of the variation in eGFR at 1-year and 13% at 5-year, with PRSs cumulatively adding 1% in both cases. PRSs were not associated with long-term graft survival. We demonstrate a small, but statistically significant association between donor and recipient PRSs and recipient graft function at 1- and 5-year post-transplant. This effect is, at present, unlikely to have clinical application and further research is required to improve PRS performance.

Keywords: eGFR; graft function; graft survival; multivariable models; polygenic risk scores.

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Conflict of interest statement

IH reports receiving research funding from MSD and Hansa Biopharma, and has ongoing consultancy agreements with Novartis, Hansa Biopharma, and Takeda. ML has received advisory and consulting fees from Bayer, Sanofi, Reata, GlaxoSmithKline, and Otsuka. GC and PC report receiving research funding relating to kidney disease genetics from Biomarin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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