Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients

Abstract

Background/Objectives: Renal transplantation is the treatment of choice for patients with end-stage renal disease. In the last decade, the number of older renal transplant recipients has significantly increased. However, these patients are at a higher risk of developing post-transplant complications. Therefore, identifying the suitable biomarkers to predict which older patients are at risk of complications is crucial. Cellular senescence could provide insights into the increased vulnerability in this population and guide personalized post-transplant care. Methods: This preliminary study involved biopsies from 25 patients with renal allograft rejection and 18 patients without rejection, further divided into older (50–65 years) and younger (29–40 years) groups. Biopsies were collected at different time points after transplantation, and rejection was classified according to the histological Banff 07 criteria. Additionally, immunohistochemistry for the markers of cellular senescence, p27kip1 and p16INK4a, was performed. Results: We observed that the number of p27kip1-positive glomeruli was higher in the older patients with rejection compared to the younger patients with rejection, and a similar pattern was found in the patients without rejection. However, the number of p27kip1-positive tubules was higher in the older patients with rejection compared to the younger patients with rejection, as well as compared to both the older and younger patients without rejection. Tubular p16INK4a expression was not significantly different in the older patients with rejection compared to the younger patients with rejection, and the same pattern was observed in the patients without rejection. However, it was increased in the older patients with rejection in comparison to the older patients without rejection. Conclusions: Our preliminary data suggest the strong potential of both p16INK4a and p27kip1 as biomarkers of renal graft rejection, particularly in older renal transplant recipients.

Keywords

• kidney transplantation
• allograft rejection
• age
• senescence
• p16^INK4a
• p27^kip1