Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

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 (<i>P</i> < 0.001), eGFR PRS (<i>P</i> < 0.001), and intracranial aneurysm PRS (<i>P</i> = 0.01), along with <i>recipient</i> eGFR PRS (<i>P</i> = 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.

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Publication Details

Journal
Transplant International
Published
2025-03-04
DOI
https://doi.org/10.3389/ti.2025.14171
Primary Topic
Renal Transplantation Outcomes and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Salla Markkinen, Jukka Partanen, Elhussein A. Elhassan, Kati Hyvärinen et al.
Transplant International
Renal Transplantation Outcomes and Treatments
article

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Salla Markkinen, Jukka Partanen, Elhussein A. Elhassan, Kati Hyvärinen, Graham M. Lord, Conall M. O’Seaghdha, Gianpiero L. Cavalleri, Matthew B. Lanktree, Ilkka Helanterä, Katherine A. Benson, Peter J. van der Most, Edmund Gilbert, Kane E. Collins, Vincent Mauduit, Brendan J. Keating, Ajay K. Israni, Stephen F. Madden, Amy Jayne McKnight, Pamala A. Jacobson, Claire Hill, Martin H. de Borst, Peter J. Conlon, Sophie Limou, Alexander P. Maxwell, Weihua Guan
article en

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 (<i>P</i> < 0.001), eGFR PRS (<i>P</i> < 0.001), and intracranial aneurysm PRS (<i>P</i> = 0.01), along with <i>recipient</i> eGFR PRS (<i>P</i> = 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.

Transplant InternationalVol. 38
École Centrale de Nantes (FR), Queen's University Belfast (GB), University of Minnesota (US), University Medical Center Groningen (NL), University of Helsinki (FI), Royal College of Surgeons in Ireland (IE), Inserm (FR), Science Foundation Ireland (IE), University of Groningen (NL), King's College London (GB), Ollscoil na Gaillimhe – University of Galway (IE), Helsinki University Hospital (FI), Finnish Red Cross (FI), Beaumont Hospital (IE), Population Health Research Institute (CA), Cancer Research And Biostatistics (US), Molecular Medicine Ireland (IE), Netherlands School of Public Administration (NL), Impact (CA), Canadian Society of Nephrology (CA), Center for Research in Transplantation and Translational Immunology, The University of Texas Medical Branch at Galveston (US), St. Joseph’s Healthcare Hamilton (CA), University of Pennsylvania (US), McMaster University (CA)
Medical Research Council
Good health and well-being
Openalex Percentile: Top 93%
Renal Transplantation Outcomes and Treatments
DOIOpen Access PDFOpenAlex
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