高龄亲属活体供肾在青年受体内病理学改变的长期研究

方佳丽; 陈正; 马俊杰; 李光辉; 徐璐; 张磊; 尹威; 赖兴强; 郭予和; 张异蕊; 潘光辉

doi:10.3969/j.issn.1674-7445.2019.02.010

高龄亲属活体供肾在青年受体内病理学改变的长期研究

doi: 10.3969/j.issn.1674-7445.2019.02.010

510260 广州医科大学附属第二医院移植科

基金项目:

广东省科技计划项目 2014A020212319

广州市卫生医药卫生科技一般引导项目 20151A01009

详细信息

作者简介:
方佳丽，女，1980年生，硕士，主治医师，研究方向为器官移植，Email：rainfong@126.com

通讯作者:
陈正，男，1974年生，博士，主任医师，研究方向为器官移植，Email：docchenzheng@163.com

中图分类号: R617, R602
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出版历程
- 收稿日期: 2018-12-14
- 网络出版日期: 2021-01-19
- 刊出日期: 2019-03-15

Long-term study of pathological changes of living renal grafts from elderly relatives in young recipients

Department of Transplantation, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China

More Information

Corresponding author: Chen Zheng, Email: docchenzheng@163.com

摘要

摘要: 目的通过长期病理随访探讨青年受体接受高龄亲属活体供肾肾移植的安全性。方法根据供体年龄不同，将28例青年受体分为观察组（14例，高龄供体）和对照组（14例，中青年供体）。分别比较两组移植肾术后7年的存活情况及术后各时间点的血清肌酐（Scr）水平；比较两组在零时、术后6个月、术后7年移植肾活组织检查（活检）的慢性病理损伤评分；比较两组受体术后6个月、术后7年移植肾间质纤维化相关指标结缔组织生长因子（CTGF）、转化生长因子（TGF）-β、层黏连蛋白（LN）、纤维连接蛋白（FN）及细胞衰老相关指标细胞间连接蛋白（Cx）43及哺乳动物雷帕霉素靶蛋白（mTOR）的表达量。结果观察组和对照组移植肾术后7年存活率分别为78.5%和92.8%，差异无统计学意义（P > 0.05）。观察组、对照组术后7 d Scr水平分别为190、160 μmol/L，术后1个月Scr水平分别为170、125 μmol/L，观察组术后各时间点的Scr水平均高于对照组，差异均有统计学意义（均为P > 0.05）。观察组移植肾组织零时活检的慢性病理损伤总评分明显高于对照组（P > 0.05），但两组术后7年的慢性病理损伤总评分无明显差异（P > 0.05）。观察组和对照组组内各时间点比较，术后7年活检的慢性病理损伤总评分均高于零时活检及术后6个月活检的慢性病理损伤总评分（均为P > 0.05）。两组术后7年移植肾组织中CTGF、TGF-β、LN、FN、mTOR、Cx43表达量的比较差异均无统计学意义（均为P > 0.05）。结论长期随访结果显示青年受体接受高龄供肾与接受中青年供肾的病理学改变相似，从病理学角度考虑青年受体接受高龄供肾是安全可行的。
- 肾移植 /
- 高龄供体 /
- 边缘供体 /
- 慢性病理损伤评分 /
- 肾小球硬化 /
- 肾小动脉硬化 /
- 肾间质纤维化 /
- 细胞外基质 /
- 肾脏衰老 /
- 血清肌酐
Abstract: Objective To investigate the safety of young recipients undergoing living donor renal transplantation from elderly relative donors through long-term follow-up of the pathological changes. Methods According to the age of donors, 28 young recipients were divided into the observation group (n=14, elderly donors) and control group (n=14, young and middle-aged donors). The 7-year survival after renal transplantation, the serum creatinine (Scr) levels at various postoperative time points were compared between two groups. The chronic pathological injury scores of renal allograft biopsy at time-zero, postoperative 6-month and 7-year were compared between two groups. The expression levels of renal interstitial fibrosis indicators connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, laminin (LN), fibronectin (FN), cell senescence indicators intercellular connexin (Cx)-43 and mammalian target of rapamycin (mTOR) at postoperative 6-month and 7-year were compared between two groups. Results The 7-year survival rates in the observation and control groups were 78.5% and 92.8% with no statistical significance (P > 0.05). In the observation and control groups, the levels of Scr were 190 and 160 μmol/L at the postoperative 7 d, and 170 and 125 μmol/L at postoperative 1 month. At each postoperative time point, the levels of Scr in the observation group were significantly higher than those in the control group (all P > 0.05). The total chronic pathological injury scores of renal transplant biopsy at time-zero in the observation group was significantly higher than that in the control group (P > 0.05), whereas the total chronic pathological injury scores at postoperative 7-year did not significantly differ between two groups (P > 0.05). Within either group, the total chronic pathological injury scores at postoperative 7-year was remarkably higher than those at time-zero and postoperative 6-month (both P < 0.05). The expression levels of CTGF, TGF-β, LN, FN, mTOR, Cx43 of renal transplant tissue at postoperative 7-year did not significantly differ between two groups (all P > 0.05). Conclusions The long-term follow-up outcomes demonstrate that the pathological changes of young recipients undergoing renal transplantation from elderly donors are similar to those from young and middle-aged donors. It is safe and feasible for young recipients to undergo renal transplantation from elderly donors in the pathological perspective.
- Renal transplantation /
- Elderly donor /
- Edge donor /
- Chronic pathological injury score /
- Glomerular sclerosis /
- Renal arteriolosclerosis /
- Renal interstitial fibrosis /
- Extracellular matrix /
- Kidney aging /
- Serum creatinine

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图 1 两组受体肾移植术后Scr水平的变化

Figure 1. Changes of Scr level of recipients in two groups after renal transplantation

下载: 全尺寸图片幻灯片

图 2 两组受体术后7年移植肾组织中肾间质纤维化及细胞衰老指标的比较

A图和B图示观察组和对照组的CTGF表达（免疫组化，×400）；C图和D图示观察组和对照组的FN表达（免疫组化，×400）；E图和F图示观察组和对照组的TGF-β表达（免疫组化，×400）；G图和H图示观察组和对照组的mTOR表达（免疫组化，×400）；I图和J图示观察组和对照组的LN表达（免疫组化，×400）；K图和L图示观察组和对照组的Cx 43表达（免疫组化，×400）；M图为两组各指标表达量的比较

Figure 2. Comparison of renal interstitial fibrosis and cell senescence indexes for transplanted kidney tissues of recipients between two groups at 7 years after surgery

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表 1 两组受体移植肾组织的慢性病理损伤评分的比较

Table 1. Comparison of chronic pathological injury scores for transplanted kidney tissues of recipients between two groups(x±s, score)

肾脏慢性病理损伤指标	观察组	对照组	P值
零时	（n=14）	（n=14）
总评分	5（3~7）	2（1~5）	0.005
肾小球病变	2（1~5）	2（1~3）	0.024
肾小管病变	1（0~2）	1（0~2）	0.097
肾小球硬化比例	0.151（0.022~0.268）	0.071（0.025~0.116）	0.190
肾小动脉硬化指数	0.668（0.569~0.742）	0.655（0.555~0.737）	0.800
术后6个月	（n=13）	（n=14）
总评分	5（2~7）	3（2~4）	0.199
肾小球病变	2（1~4）	2（1~3）	0.243
肾小管病变	1（0~2）	2（1~2）	0.395
肾小球硬化比例	0.188（0.041~0.307）	0.100（0.097~0.220）	0.544
肾小动脉硬化指数	0.610（0.551~0.744）	0.673（0.541~0.779）	0.414
术后7年	（n=11）	（n=13）
总评分	8（5~11）	7（4~10）	0.590
肾小球病变	4（2~5）	4（2~5）	0.810
肾小管病变	3（2~4）	2（1~2）	0.113
肾小球硬化比例	0.388（0.221~0.566）	0.325（0.113~0.525）	0.769
肾小动脉硬化指数	0.661（0.548~0.779）	0.681（0.597~0.749）	0.906

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