Raschenberger Julia, Kollerits Barbara, Ritchie James, Lane Beverley, Kalra Philip A, Ritz Eberhard, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Vascular Research Group, The University of Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
Sci Rep. 2015 Jul 7;5:11887. doi: 10.1038/srep11887.
Chronic kidney disease (CKD) is a highly progressive disease. We studied the association between relative telomere length (RTL) and CKD progression and tested whether this association is modified by smoking and diabetes mellitus. RTL was measured by qPCR in two prospective cohort studies, the MMKD-Study (n = 166) and the CRISIS-Study (n = 889) with a median follow-up of 4.5 and 2.8 years, respectively. Progression was defined as doubling of baseline serum creatinine (MMKD-Study) and/or end stage renal disease (both studies). 59 and 105 of the patients from MMKD and CRISIS experienced a progression of CKD. Mean standardized pooled RTL was 0.74 ± 0.29. In the meta-analysis shorter RTL at baseline showed a borderline association with CKD progression (HR = 1.07 [95%CI 1.00-1.15]; p = 0.06). We observed an effect modification of RTL and CKD progression by smoking and diabetes (p-values of interaction p = 0.02 and p = 0.09, respectively). Each 0.1 unit shorter RTL was significantly associated with an increased hazard for CKD progression in active-smokers by 44% (HR = 1.44 [1.16-1.81]; p = 0.001) and in patients with diabetes mellitus by 16% (HR = 1.16 [1.01-1.34]; p = 0.03). Estimates were adjusted for baseline age, sex, proteinuria and GFR. This study in two independent cohorts reinforces that RTL is a marker and potentially a pathogenetic factor for CKD progression.
慢性肾脏病（CKD）是一种高度进展性疾病。我们研究了相对端粒长度（RTL）与CKD进展之间的关联，并测试了吸烟和糖尿病是否会改变这种关联。在两项前瞻性队列研究中，即MMKD研究（n = 166）和CRISIS研究（n = 889）中，分别采用qPCR测量RTL，中位随访时间分别为4.5年和2.8年。进展定义为基线血清肌酐翻倍（MMKD研究）和/或终末期肾病（两项研究）。MMKD和CRISIS研究中分别有59例和105例患者出现CKD进展。平均标准化合并RTL为0.74±0.29。在荟萃分析中，基线时较短的RTL与CKD进展存在临界关联（HR = 1.07 [95%CI 1.00 - 1.15]；p = 0.06）。我们观察到吸烟和糖尿病对RTL与CKD进展有效应修饰作用（交互作用p值分别为0.02和0.09）。RTL每缩短0.1个单位，当前吸烟者发生CKD进展的风险显著增加44%（HR = 1.44 [1.16 - 1.81]；p = 0.001），糖尿病患者发生CKD进展的风险增加16%（HR = 1.16 [1.01 - 1.34]；p = 0.03）。估计值已根据基线年龄、性别、蛋白尿和肾小球滤过率进行了调整。这项在两个独立队列中的研究强化了RTL是CKD进展的一个标志物，并且可能是一个致病因素。
