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Kidney Week

Abstract: TH-PO647

Recipient Polygenic Burden as a Predictor of Kidney Transplant Outcome

Session Information

  • Transplantation: Basic
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Collins, Kane Edmund, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Gilbert, Edmund H., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Lord, Graham M., King's College London, London, London, United Kingdom
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Ireland
Background

The clinical predictors of transplant outcome have been well established and include HLA mismatch, donor age, era of transplantation, immunosuppressive regimen, and recipient blood pressure. Polygenic burden can be quantified using a Polygenic Risk Score (PRS), which estimates the cumulative effect of common genetic variation on an individual’s disease status Polygenic burden has been demonstrated to have an impact on kidney function, but the impact of polygenic burden on kidney graft function is less clear. It has also been shown that polygenic burden can predict certain transplant outcomes including the development of Non Melanoma Skin Cancer. Here, we investigate the role of polygenic burden in kidney transplant recipients on transplant outcome.

Methods

We utilised 2,122 genotyped donor-recipient pairs from across the UK and Ireland and 5,519 ancestry matched controls. We calculated PRSs for eGFR, albuminuria, and hypertension from large, publicly available summary statistics from populations of European ancestry. We compared PRSs between recipients and the healthy controls. We also investigated the differences in transplant outcome between the individuals with high polygenic burden (defined as top 20% of distribution) for each trait and those with low polygenic burden (bottom 80%).

Results

Recipients had lower polygenic burden for reduced eGFR (p-value: 7.9e-4) than healthy controls. There was no statistically significant difference in graft survival or graft function at 1-year post-transplant between individuals with high and low polygenic burden. However, there was a significant difference in graft function at 5 years’ post-transplant between the high and low polygenic burden individuals (Odds Ratio: 16.2, p-value: 0.048).

Conclusion

Polygenic burden for eGFR has an impact on graft function at 5 years’ post-transplant, but other traits do not appear to have a significant effect. This is in line with what previous studies have found.

Funding

  • Government Support – Non-U.S.