Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Area of Science:

• Nephrology
• Genetics
• Transplantation Immunology

Background:

• Kidney transplant outcomes are influenced by various factors, but significant unexplained variability persists.
• Donor and recipient genetic predispositions may contribute to this variability in graft function.

Purpose of the Study:

• To investigate the association between polygenic risk scores (PRSs) for kidney function-related traits in donors and recipients and kidney transplant outcomes.
• To determine if PRSs explain any of the unexplained variability in graft function post-transplantation.

Main Methods:

• Assembled a cohort of 6,060 living and deceased kidney donor-recipient pairs.
• Calculated PRSs for kidney function-related traits in both donors and recipients.
• Assessed the association of PRSs with recipient estimated glomerular filtration rate (eGFR) at 1- and 5-year post-transplant and graft failure.

Main Results:

• Donor hypertension PRS, eGFR PRS, and intracranial aneurysm PRS, along with recipient eGFR PRS, were associated with 1-year post-transplant eGFR.
• PRSs cumulatively explained an additional 1% of variation in eGFR at both 1- and 5-year post-transplant, beyond clinical factors.
• No significant association was found between PRSs and long-term graft survival.

Conclusions:

• Donor and recipient PRSs demonstrate a small but statistically significant association with early graft function (1- and 5-year post-transplant eGFR).
• The current predictive power of PRSs for kidney transplant outcomes is limited and unlikely to have immediate clinical utility.
• Further research is needed to enhance PRS performance for potential clinical application in transplantation.