Stefanidis Ioannis, Voliotis Georgios, Papanikolaou Vassilios, Chronopoulou Ioanna, Eleftheriadis Theodoros, Kowald Axel, Zintzaras Elias, Tsezou Aspasia
Clinic of Nephrology, University of Thessaly, Larissa, Greece.
Laboratory of Cytogenetics and Molecular Genetics, University of Thessaly, Larissa, Greece.
Artif Organs. 2015 Sep;39(9):756-64. doi: 10.1111/aor.12453. Epub 2015 Apr 20.
Telomere shortening to a critical limit is associated with replicative senescence. This process is prevented by the enzyme telomerase. Oxidative stress and chronic inflammation are factors accelerating telomere loss. Chronic hemodialysis, typically accompanied by oxidative stress and inflammation, may be also associated with replicative senescence. To test this hypothesis, we determined telomere length and telomerase activity in peripheral blood mononuclear cells (PBMCs) in a cross-sectional study. Hemodialysis patients at the University Hospital Larissa and healthy controls were studied. Telomere length was determined by the TeloTAGGG Telomere Length Assay and telomerase activity by Telomerase PCR-ELISA (Roche Diagnostics GmbH, Mannheim, Germany). We enrolled 43 hemodialysis patients (17 females; age 65.0 ± 12.7 years) and 23 controls (six females; age 62.1 ± 15.7 years). Between the two groups, there was no difference in telomere length (6.95 ± 3.25 vs. 7.31 ± 1.96 kb; P = 0.244) or in telomerase activity (1.82 ± 2.91 vs. 2.71 ± 3.0; P = 0.085). Telomere length correlated inversely with vintage of hemodialysis (r = -0.332, P = 0.030). In hemodialysis patients, positive telomerase activity correlated with telomere length (r = 0.443, P = 0.030). Only age, and neither telomere length nor telomerase activity, was an independent survival predictor (hazard ratio 1.116, 95% confidence interval 1.009-1.234, P = 0.033). In this study, telomere length and telomerase activity in PBMCs are not altered in hemodialysis patients compared with healthy controls. Long duration of hemodialysis treatment is associated with telomere shortening and positive telomerase activity with an increased telomere length in PBMCs of hemodialysis patients. The underlying mechanism and clinical implications of our findings require further investigation.
端粒缩短至临界极限与复制性衰老相关。端粒酶可阻止这一过程。氧化应激和慢性炎症是加速端粒丢失的因素。慢性血液透析通常伴有氧化应激和炎症，也可能与复制性衰老有关。为验证这一假设，我们在一项横断面研究中测定了外周血单个核细胞（PBMC）中的端粒长度和端粒酶活性。研究对象为拉里萨大学医院的血液透析患者和健康对照者。端粒长度通过TeloTAGGG端粒长度检测法测定，端粒酶活性通过端粒酶PCR-ELISA法（德国曼海姆罗氏诊断有限公司）测定。我们纳入了43例血液透析患者（17例女性；年龄65.0±12.7岁）和23例对照者（6例女性；年龄62.1±15.7岁）。两组之间，端粒长度（6.95±3.25对7.31±1.96 kb；P = 0.244）或端粒酶活性（1.82±2.91对2.71±3.0；P = 0.085）无差异。端粒长度与血液透析时间呈负相关（r = -0.332，P = 0.030）。在血液透析患者中，端粒酶活性阳性与端粒长度相关（r = 0.443，P = 0.030）。只有年龄是独立的生存预测因素，端粒长度和端粒酶活性均不是（风险比1.116，95%置信区间1.009 - 1.234，P = 0.033）。在本研究中，与健康对照者相比，血液透析患者PBMC中的端粒长度和端粒酶活性未改变。长期血液透析治疗与端粒缩短以及血液透析患者PBMC中端粒酶活性阳性且端粒长度增加有关。我们研究结果的潜在机制和临床意义需要进一步研究。
