Tubular Cell Senescence in the Donated Kidney Predicts Allograft Function, but Not Donor Remnant Kidney Function, in Living Donor Kidney Transplantation
Tubular Cell Senescence in the Donated Kidney Predicts Allograft Function, but Not Donor Remnant Kidney Function, in Living Donor Kidney Transplantation
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在活体供肾移植中，供肾中的肾小管细胞衰老可预测同种异体移植物的功能，但不能预测供体残余肾的功能
DOI：
10.1159/000485845
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发表时间：
2017
影响因子：
4.2
通讯作者：
Minamino Tetsuo
中科院分区：
文献类型：
--
作者：
Sofue Tadashi;Kushida Yoshio;Ozaki Taro;Moritoki Masahiro;Nishijima Yoko;Ohsaki Hiroyuki;Ueda Nobufumi;Kakehi Yoshiyuki;Nishiyama Akira;Minamino Tetsuo
背景边缘供者的肾脏是否适合活体肾移植尚不确定。在已故供体肾脏中，肾小管细胞衰老影响同种异体移植的功能。然而，细胞衰老的程度在一个活体供体肾脏的边缘因素尚未报道。在这项研究中，我们通过一项前瞻性观察性临床研究评估了小管细胞衰老与同种异体移植肾和残肾功能的关系。方法对38例活体肾移植进行前瞻性分析。从植入前肾活检获得的组织切片进行p16 INK4a免疫染色，以指示细胞衰老。在尿液和血液样本中分析了各种肾脏生物标志物。结果38例献血者中有21例存在边缘性因素。严重的肾小管衰老发现在活体供体重叠的边缘标准。活体肾小管衰老与供体年龄和移植后1年受者肾功能下降有显著关系（β= -0.281; p= 0.050），而与供体年龄无关（β= -0.281; p= 0.050），但不影响捐赠后残余肾功能。移植前供体预估的肾小球滤过率和高血压在预测高肾小管衰老方面没有显示出显著的曲线下面积（AUC）。高血浆可溶性α - klotho水平与低小管细胞衰老的较高预测值相关，AUC为0.78 （95% CI 0.62-0.93; p< 0.01）。结论供肾小管核p16染色率是异体移植肾功能的预测指标，而不是供肾残肾功能的预测指标。检测小管细胞衰老有助于选择合适的活体供体候选人。
BackgroundIt is uncertain whether kidneys from marginal donors are suitable for live kidney transplantation. In deceased donor kidneys, tubular cell senescence affects allograft function. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported. In this study, we assessed the association of tubular cell senescence with allograft and remnant kidney function by a prospective observational clinical study.MethodsThirty-eight living donor kidney transplantations were analyzed prospectively. Tissue sections obtained from preimplantation kidney biopsies were immunostained for p16 INK4a to indicate cell senescence. Various kidney biomarkers were analyzed in urine and blood samples.ResultsOf 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 function at 1 year after transplantation independently of donor age (β=–0.281; p= 0.050) but did not affect remnant kidney function after donation. Pretransplantation donor pre-estimated glomerular filtration rate and hypertension did not show a significant area under the curve (AUC) for prediction of high tubular senescence. High plasma levels of soluble αKlotho were associated with a higher predictive value for low tubular cell senescence with an AUC of 0.78 (95% CI 0.62–0.93; p< 0.01).ConclusionsThe nuclear p16-staining rate in donated kidney tubules is a predictor for allograft kidney function but not donor remnant kidney function. Detection of tubular cell senescence may facilitate selection of appropriate living donor candidates.
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