Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation
Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation
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DOI：
10.1111/j.1474-9726.2008.00398.x
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发表时间：
2008-08-01
期刊：
影响因子：
7.8
通讯作者：
Mayer, Gert
中科院分区：
文献类型：
--
作者：
Koppelstaetter, Christian;Schratzberger, Gabriele;Mayer, Gert
尽管供者的实际年龄是肾移植术后长期预后的最有效预测因素，但它并不包括年龄过程本身的个体差异。因此，我们假设，从零时活检中的细胞衰老标记物推导出的生物器官年龄估计值将具有更高的预测价值。端粒长度和细胞周期抑制剂CDKN2A（p16INK4a）和CDKN1A（p21WAF1）的mRNA表达水平在54例患者的植入前活检中进行了评估，并确定了这些和各种其他临床参数与1年后血清肌酐的相关性。在线性回归分析中，CDKN2A是最好的单一预测因子，其次是供体年龄和端粒长度。多元线性回归分析显示，CDKN2A值和供体年龄的组合产生了更高的预测值，血清肌酐移植后1年。我们的结论是，分子衰老标记物CDKN2A与供体实际年龄相结合预测1年后移植肾功能明显优于供体实际年龄。
Although chronological donor age is the most potent predictor of long-term outcome after renal transplantation, it does not incorporate individual differences of the aging-process itself. We therefore hypothesized that an estimate of biological organ age as derived from markers of cellular senescence in zero hour biopsies would be of higher predictive value. Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre-implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined. In a linear regression analysis, CDKN2A turned out to be the best single predictor followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values for serum creatinine 1 year after transplantation. We conclude that the molecular aging marker CDKN2A in combination with chronological donor age predict renal allograft function after 1 year significantly better than chronological donor age alone.