Abstract:
Telomere length (TL) is an important biological variable that can influence a variety of disease-related complex traits as well as host-environment interactions such as drug and nutritional responses. Chronic kidney disease (CKD) is a common global health challenge especially with the currently aging world population. We conducted a PubMed database search according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines for systematic reviews. Studies in adults (18 years and above) in which TL was determined and correlated with CKD, renal traits, and function were included, while animal model studies were excluded. Nine studies comprising 7829 participants, published between 2005 and 2016, met the inclusion criteria. These included eight observational studies (six being prospective), and one clinical trial. Participants in two studies were diabetic patients with varying stages of CKD, and nondialysis chronic glomerulonephritis CKD patients in two other studies. TL measurements used polymerase chain reaction in five studies, terminal restriction fragmentation in three studies, and quantitative fluorescence in situ hybridization in one study. Short TL was independently associated with increased risk of prevalent microalbuminuria in diabetic men with CKD (p = 0.007). Among CKD patients with heterogeneous etiologies, however, there was an unadjusted lower risk (p < 0.001). Short TL was significantly associated with CKD progression among smokers (p = 0.001) and diabetic patients (p = 0.03). On the other hand, long TL was paradoxically associated with longer diagnosed duration of moderate CKD. We postulate that shortening TL might be associated with CKD prevalence/occurrence or declining kidney function, but this association is likely offset by the cellular telomere reparative process in those surviving longer with CKD. This systematic review underscores the need for future omics and human genetics research to delineate the contribution of TL to CKD, renal dysfunction, and related health outcomes. Telomeres and telomerase activity hold great promise for CKD risk stratification and personalized medicine.
摘要:
端粒长度(TL)是一个重要的生物学变量,可以影响各种疾病相关的复杂性状以及宿主-环境相互作用,如药物和营养反应。慢性肾脏病(CKD)是一个共同的全球健康挑战,尤其是随着当前世界人口老龄化。我们根据系统评价的首选报告项目和系统评价的荟萃分析(PRISMA)指南进行了PubMed数据库搜索。在成人(18岁及以上)的研究中,TL被确定并与CKD相关,肾性状,和功能被包括在内,而动物模型研究被排除在外。九项研究包括7829名参与者,在2005年至2016年期间发布,符合纳入标准。其中包括八项观察性研究(六项是前瞻性的),还有一项临床试验.两项研究的参与者是患有不同阶段CKD的糖尿病患者,和非透析慢性肾小球肾炎CKD患者在另外两项研究中。TL测量在五项研究中使用聚合酶链反应,三项研究中的末端限制性片段化,和定量荧光原位杂交的研究。短TL与CKD糖尿病男性中微量白蛋白尿的风险增加独立相关(p=0.007)。在具有异质性病因的CKD患者中,然而,风险较低(p<0.001).在吸烟者(p=0.001)和糖尿病患者(p=0.03)中,短TL与CKD进展显着相关。另一方面,长TL与中度CKD诊断持续时间较长矛盾.我们假设缩短TL可能与CKD患病率/发生或肾功能下降有关。但在CKD存活时间较长的人群中,这种关联可能被细胞端粒修复过程所抵消.这篇系统综述强调了未来组学和人类遗传学研究的必要性,以描绘TL对CKD的贡献。肾功能不全,和相关的健康结果。端粒和端粒酶活性为CKD风险分层和个性化医疗提供了广阔的前景。