Collins Kane E, Gilbert Edmund, Mauduit Vincent, Benson Katherine A, Elhassan Elhussein A E, O'Seaghdha Conall, Hill Claire, McKnight Amy Jayne, Maxwell Alexander P, van der Most Peter J, de Borst Martin H, Guan Weihua, Jacobson Pamala A, Israni Ajay K, Keating Brendan J, Lord Graham M, Markkinen Salla, Helanterä Ilkka, Hyvärinen Kati, Partanen Jukka, Madden Stephen F, Lanktree Matthew B, Limou Sophie, Cavalleri Gianpiero L, Conlon Peter J
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
The Science Foundation Ireland FutureNeuro Centre of Excellence, Dublin, Ireland.
Transpl Int. 2025 Mar 4;38:14171. doi: 10.3389/ti.2025.14171. eCollection 2025.
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 ( < 0.001), eGFR PRS ( < 0.001), and intracranial aneurysm PRS ( = 0.01), along with eGFR PRS ( = 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.
肾移植结果受供体和受体的年龄、性别、人类白细胞抗原（HLA）错配、供体类型、抗排斥药物依从性和疾病复发的影响，但移植结果的变异性仍无法解释。我们假设，供体和受体与肾功能相关性状的多基因负担也可能影响移植肾功能。我们组建了一个由6060对活体和已故肾供体-受体组成的队列。我们计算了供体和受体中与肾功能相关性状的多基因风险评分（PRS）。我们研究了这些PRS与移植后1年和5年时受体的估算肾小球滤过率（eGFR）以及移植失败之间的关联。供体：高血压PRS（<0.001）、eGFR PRS（<0.001）和颅内动脉瘤PRS（=0.01），以及受体eGFR PRS（=0.001）与移植后1年时的eGFR相关。临床因素解释了1年时eGFR变异的25%和5年时的13%，在这两种情况下，PRS累计增加1%。PRS与长期移植存活无关。我们证明，供体和受体的PRS与移植后1年和5年时受体的移植肾功能之间存在微小但具有统计学意义的关联。目前，这种效应不太可能应用于临床，需要进一步研究以提高PRS的性能。
