Abstract: TH-PO965

Tubular Cell Senescence in the Donated Kidney Predicts Allograft Functions, but Not Donor Remnant Kidney Functions, in Living Donor Kidney Transplantation

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Sofue, Tadashi, Kagawa University, Kagawa, Japan
  • Kushida, Yoshio, Kagawa University, Kagawa, Japan
  • Ozaki, Taro, Kagawa University, Kagawa, Japan
  • Moritoki, Masahiro, Kagawa University, Kagawa, Japan
  • Nishijima, Yoko, Kagawa University, Kagawa, Japan
  • Nishiyama, Akira, Kagawa University, Kagawa, Japan
  • Minamino, Tetsuo, Kagawa University, Kagawa, Japan
Background

It is uncertain whether kidneys from marginal donors are suitable for living kidney transplantation. In deceased donor kidneys, tubular cell senescence in the donated kidney is reported to affect allograft functions. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported so far. In this study, we assessed the association of tubular senescence with allograft and remnant kidney functions in living donor kidney transplantation by a prospective observational clinical study.

Methods

Thirty-eight living donor kidney transplantations were analyzed prospectively. Tissue sections obtained from pre-implantation kidney biopsies were immunostained for p16INK4a to indicate tubular senescence. Various kidney biomarkers were analyzed in urine and blood samples. The protocols and informed consent forms were reviewed and approved by the Ethics Committee of Kagawa University (#H22-056) and registered in the UMIN Clinical Trials Registry (UMIN000004905).

Results

Of the 38 donors, 21 had marginal factors. Severe tubular senescence was found in living donors with overlapping marginal criteria. Tubular senescence in living donor kidneys was significantly related to donor age and lower recipient kidney functions at 1 year after transplantation independently of donor age (β = -0.281; P = 0.050), but did not affect remnant kidney functions after donation. Pre-transplant donor factors, such as pre-eGFR, hypertension, systolic blood pressure, and albuminuria, did not show any significant AUC for prediction of high tubular cell senescence. High plasma soluble αKlotho levels were associated with a higher predictive value for low tubular cell senescence with an area under the curve of 0.78 (95% confidence interval 0.62–0.93; P < 0.01).

Conclusion

The nuclear p16-staining rate in donated kidney tubules is a predictor for allograft kidney functions, but not donor remnant kidney functions in living donor kidney transplantation. Detection of tubular cell senescence may facilitate selection of appropriate living donor candidates.

Funding

  • Government Support - Non-U.S.