Gurung Resham Lal, M Yiamunaa, Liu Sylvia, Liu Jian-Jun, Lim Su Chi
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Diabetes Centre, Khoo Teck Puat Hospital, Singapore.
Kidney Int Rep. 2017 Dec 16;3(3):592-601. doi: 10.1016/j.ekir.2017.12.005. eCollection 2018 May.
Telomere length, a marker for biological aging, is implicated with diabetic kidney disease (DKD); however, the association between telomere length and albuminuria progression among Asian patients with type 2 diabetes (T2D) is not well understood. Here, we aim to study whether leukocyte telomere length (LTL) may independently predict albuminuria progression in patients with T2D with preserved renal filtration function (estimated GFR >60 ml/min per 1.73 m and urine albumin-to-creatinine ratio [uACR] <300 mg/g).
The baseline LTL was measured by real-time polymerase chain reaction in the SMART2D cohort ( = 691) with a median follow-up of 3 years. Albuminuria progression was defined as a change in albuminuria category to a higher category and at least 30% increase in uACR from baseline in 3 years.
Progressors ( = 123) had significantly shorter median LTL compared with nonprogressors ( = 568) (0.58 [0.38-0.79] vs. 0.62 [0.45-0.88], = 0.039). Compared with subjects with longer LTL (fourth quartile), subjects with shorter LTL (first quartile) had 1.93-fold (1.04-3.60, = 0.038) increased risk for albuminuria progression after adjustment for traditional risk factors. The association of LTL with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria (odds ratio [OR]: 1.54; 95% confidence interval [CI]: 1.02-2.32; = 0.042 vs. OR: 1.13; 95% CI: 0.91-1.40; = 0.263 per 1-SD decrement in natural log-transformed LTL).
Therefore, our results demonstrated that in patients with T2D with preserved renal filtration function, LTL predicts albuminuria progression beyond traditional risk factors, suggesting LTL may be novel biomarker for DKD progression.
端粒长度是生物衰老的一个标志物,与糖尿病肾病(DKD)有关;然而,亚洲2型糖尿病(T2D)患者中端粒长度与蛋白尿进展之间的关联尚未完全明确。在此,我们旨在研究白细胞端粒长度(LTL)是否可独立预测肾滤过功能正常(估计肾小球滤过率>60 ml/min/1.73 m²且尿白蛋白与肌酐比值[uACR]<300 mg/g)的T2D患者的蛋白尿进展情况。
在SMART2D队列(n = 691)中通过实时聚合酶链反应测量基线LTL,中位随访时间为3年。蛋白尿进展定义为蛋白尿类别转变为更高类别且3年内uACR较基线至少增加30%。
进展者(n = 123)的中位LTL显著短于非进展者(n = 568)(0.58 [0.38 - 0.79] 对 0.62 [0.45 - 0.88],P = 0.039)。与LTL较长(第四四分位数)的受试者相比,LTL较短(第一四分位数)的受试者在调整传统危险因素后蛋白尿进展风险增加1.93倍(1.04 - 3.60,P = 0.038)。LTL与微量白蛋白尿至大量白蛋白尿进展的关联强于其与正常白蛋白尿至微量白蛋白尿的关联(优势比[OR]:1.54;95%置信区间[CI]:1.02 - 2.32;P = 0.042 对 OR:1.13;95% CI:0.91 - 1.40;P = 0.263,自然对数转换后的LTL每降低1个标准差)。
因此,我们的结果表明,在肾滤过功能正常的T2D患者中,LTL可预测超出传统危险因素的蛋白尿进展,提示LTL可能是DKD进展的新型生物标志物。