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首页> 外文期刊>Aging cell. >Cellular senescence in pretransplant renal biopsies predicts postoperative organ function.
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Cellular senescence in pretransplant renal biopsies predicts postoperative organ function.

机译：移植前肾活检中的细胞衰老可预测术后器官功能。

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Older and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post-transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of preimplantation human renal allograft biopsies ( n = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function posttransplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre-transplant CDKN2A levels ( p = 0.001) and donor age ( p = 0.004)at 6 months post-transplant. Both these markers correlated significantly with urinary protein to creatinine ratios ( p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter ( p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% ( p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% ( p = 0.001) at 1 year posttransplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome.
机译：已使用较大的和边缘的供体来弥补肾脏移植可用器官的不足。这些供体的移植后肾功能和预后通常比按时间顺序年轻的供体差。但是，某些器官可以正常运作许多年。我们假设这些器官在生物学上比表现较差的器官年轻。我们已经在一组植入前的人类肾脏同种异体移植活检（n = 75）中测试了该假设，该活检已通过实时聚合酶链反应进行了分析，用于细胞损伤和生物衰老的已知标记物的表达，包括CDKN2A，CDKN1A，SIRT2和锅1。已对这些因素进行了调查，以了解与影响移植结果（供体年龄，寒冷缺血时间）和移植后器官功能（血清肌酐水平）的传统因素的任何关联。线性回归分析表明，在移植后6个月，血清肌酐与移植前CDKN2A水平（p = 0.001）和供体年龄（p = 0.004）密切相关。这两个标志物均与尿蛋白与肌酐的比率显着相关（分别为p = 0.002和p​​ = 0.005），这是随后移植物功能障碍的有益标志物。 POT1表达也显示出与该参数的显着相关性（p = 0.05）。 CDKN2A和供体年龄的多重线性回归分析占移植后6个月血清肌酐水平变化的24.6％（p = 0.001），以及移植后1年的血清肌酐水平的23.7％（p = 0.001）。因此，这些数据表明同种异体移植生物年龄是肾移植预后的重要的新的预后决定因素。

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