The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Am J Transplant. 2019 Aug;19(8):2262-2273. doi: 10.1111/ajt.15326. Epub 2019 Mar 28.


Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.

Keywords: basic (laboratory) research/science; clinical research/practice; genetics; genomics; glomerular filtration rate (GFR); kidney transplantation/nephrology; microarray/gene array; molecular biology: DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Genetic Markers*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Glomerular Filtration Rate
  • Graft Rejection / diagnosis*
  • Graft Rejection / epidemiology
  • Graft Rejection / genetics
  • Graft Survival
  • Humans
  • Kidney / physiopathology*
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Living Donors / statistics & numerical data
  • Male
  • Middle Aged
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / epidemiology
  • Postoperative Complications / genetics
  • Prognosis
  • Retrospective Studies
  • Risk Assessment / methods*
  • Risk Factors
  • Transplant Recipients / statistics & numerical data


  • Genetic Markers