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

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...

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Main Authors: Peter Vavrinec, Jakub Krivy, Sona Sykorova, Helena Bandzuchova, Zuzana Zilinska, Diana Vavrincova-Yaghi
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/10/2338
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author Peter Vavrinec
Jakub Krivy
Sona Sykorova
Helena Bandzuchova
Zuzana Zilinska
Diana Vavrincova-Yaghi
author_facet Peter Vavrinec
Jakub Krivy
Sona Sykorova
Helena Bandzuchova
Zuzana Zilinska
Diana Vavrincova-Yaghi
author_sort Peter Vavrinec
collection DOAJ
description 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, p27<sup>kip1</sup> and p16<sup>INK4a</sup>, was performed. Results: We observed that the number of p27<sup>kip1</sup>-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 p27<sup>kip1</sup>-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 p16<sup>INK4a</sup> 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 p16<sup>INK4a</sup> and p27<sup>kip1</sup> as biomarkers of renal graft rejection, particularly in older renal transplant recipients.
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spelling doaj-art-a6d90bd9edda4d27be94179131fa5f6d2025-08-20T02:11:09ZengMDPI AGBiomedicines2227-90592024-10-011210233810.3390/biomedicines12102338Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant RecipientsPeter Vavrinec0Jakub Krivy1Sona Sykorova2Helena Bandzuchova3Zuzana Zilinska4Diana Vavrincova-Yaghi5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, SlovakiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, SlovakiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, SlovakiaNational Transplant Organization, 833 03 Bratislava, SlovakiaDepartment of Nephrology and Kidney Transplantations, University Hospital and Comenius University in Bratislava, 833 05 Bratislava, SlovakiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, SlovakiaBackground/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, p27<sup>kip1</sup> and p16<sup>INK4a</sup>, was performed. Results: We observed that the number of p27<sup>kip1</sup>-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 p27<sup>kip1</sup>-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 p16<sup>INK4a</sup> 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 p16<sup>INK4a</sup> and p27<sup>kip1</sup> as biomarkers of renal graft rejection, particularly in older renal transplant recipients.https://www.mdpi.com/2227-9059/12/10/2338kidney transplantationallograft rejectionagesenescencep16<sup>INK4a</sup>p27<sup>kip1</sup>
spellingShingle Peter Vavrinec
Jakub Krivy
Sona Sykorova
Helena Bandzuchova
Zuzana Zilinska
Diana Vavrincova-Yaghi
Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
Biomedicines
kidney transplantation
allograft rejection
age
senescence
p16<sup>INK4a</sup>
p27<sup>kip1</sup>
title Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
title_full Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
title_fullStr Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
title_full_unstemmed Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
title_short Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients
title_sort association of senescence markers with age and allograft rejection in renal transplant recipients
topic kidney transplantation
allograft rejection
age
senescence
p16<sup>INK4a</sup>
p27<sup>kip1</sup>
url https://www.mdpi.com/2227-9059/12/10/2338
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AT helenabandzuchova associationofsenescencemarkerswithageandallograftrejectioninrenaltransplantrecipients
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