肾移植受者衰老标志物与年龄及同种异体移植物排斥反应的关联

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

作者信息

Vavrinec Peter, Krivy Jakub, Sykorova Sona, Bandzuchova Helena, Zilinska Zuzana, Vavrincova-Yaghi Diana

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, Slovakia.

National Transplant Organization, 833 03 Bratislava, Slovakia.

出版信息

Biomedicines. 2024 Oct 14;12(10):2338. doi: 10.3390/biomedicines12102338.

DOI:10.3390/biomedicines12102338

PMID:39457650

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11505218/

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, p27 and p16, was performed.

RESULTS

We observed that the number of p27-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-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 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 and p27 as biomarkers of renal graft rejection, particularly in older renal transplant recipients.

摘要

背景/目的：肾移植是终末期肾病患者的首选治疗方法。在过去十年中，老年肾移植受者的数量显著增加。然而，这些患者发生移植后并发症的风险更高。因此，确定合适的生物标志物以预测哪些老年患者有并发症风险至关重要。细胞衰老可为了解该人群中增加的易损性提供见解，并指导个性化的移植后护理。

方法

这项初步研究纳入了25例肾移植排斥反应患者和18例无排斥反应患者的活检样本，进一步分为老年组（50 - 65岁）和年轻组（29 - 40岁）。在移植后的不同时间点采集活检样本，并根据组织学Banff 07标准对排斥反应进行分类。此外，还进行了细胞衰老标志物p27和p16的免疫组织化学检测。

结果

我们观察到，与有排斥反应的年轻患者相比，有排斥反应的老年患者中p27阳性肾小球的数量更多，在无排斥反应的患者中也发现了类似的模式。然而，与有排斥反应的年轻患者相比，以及与有和无排斥反应的老年及年轻患者相比，有排斥反应的老年患者中p27阳性肾小管的数量更多。与有排斥反应的年轻患者相比，有排斥反应的老年患者肾小管p16表达无显著差异，在无排斥反应的患者中也观察到相同模式。然而，与无排斥反应的老年患者相比，有排斥反应的老年患者中其表达增加。