Increased Telomere Attrition After Renal Transplantation-Impact of Antimetabolite Therapy.
Increased Telomere Attrition After Renal Transplantation-Impact of Antimetabolite Therapy.
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DOI：
10.1097/txd.0000000000000629
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发表时间：
2016-12
影响因子：
2.3
通讯作者：
Stenvinkel P
中科院分区：
文献类型：
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作者：
Luttropp K;Nordfors L;McGuinness D;Wennberg L;Curley H;Quasim T;Genberg H;Sandberg J;Sönnerborg I;Schalling M;Qureshi AR;Bárány P;Shiels PG;Stenvinkel P
尿毒症环境使慢性肾脏病（CKD）患者过早衰老。肾脏替代治疗（透析和肾移植[RTx]）或免疫抑制治疗方案对衰老生物标志物的影响几乎没有研究。在这项研究中，在接近治疗开始时和12个月后再次测量了49名透析患者和47名RTx患者全血细胞中的端粒长度。43例非CKD患者作为对照。非CKD患者的端粒显著（P ≤ 0.01）长于CKD患者。RTx患者12个月后的端粒磨损显著大于透析患者（P = 0.008）。接受霉酚酸酯（MMF）治疗的RTx患者与接受硫唑嘌呤治疗的患者相比，端粒磨损程度更大（P = 0.007）。12个月后，RTx患者的叶酸水平显著高于透析患者（P < 0.0001），而同型半胱氨酸水平则相反（P < 0.0001）。12个月后，硫唑嘌呤组的叶酸水平低于MMF组（P = 0.003）。免疫抑制治疗、端粒磨损和叶酸变化之间的关联表明甲基供体潜力、免疫抑制药物和生物衰老之间存在联系。RTx后在MMF组中观察到的端粒磨损增加是由免疫抑制治疗引起的，这一假设值得进一步关注。
The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls. Non-CKD patients had significantly (P ≤ 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P = 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P = 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P < 0.0001), whereas the opposite was true for homocysteine (P < 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P = 0.003). The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention.