Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease
Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease
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DOI：
10.1155/2019/5432453
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发表时间：
2019-07
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通讯作者：
Akifumi Onishi;H. Sugiyama;M. Kitagawa;T. Yamanari;Keiko Tanaka;Ayu Ogawa-Akiyama;Yuzuki Kano;K. Mise;Katsuyuki Tanabe;H. Morinaga;M. Kinomura;H. Uchida;J. Wada
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作者：
Akifumi Onishi;H. Sugiyama;M. Kitagawa;T. Yamanari;Keiko Tanaka;Ayu Ogawa-Akiyama;Yuzuki Kano;K. Mise;Katsuyuki Tanabe;H. Morinaga;M. Kinomura;H. Uchida;J. Wada
DNA甲基化的改变可能参与慢性肾脏病（CKD）患者的疾病进展。最近的研究表明，5-甲基-2 ′-脱氧胞苷（5 MedC）可能是DNA高甲基化的标志物。目前，尚无有关5 MedC尿液水平及其与慢性肾病进展相关性的信息。方法采用竞争性酶联免疫吸附试验（ELISA）检测308例CKD患者（中位年龄56岁，男性53.2%，肾小球肾炎51.0%）尿中5 MedC水平，并分析尿5 MedC、尿白蛋白、尿α1-微球蛋白（α 1-MG）与CKD相关实验室指标的关系。对患者随访3年，以前瞻性方式评价肾脏终点。结果CKD晚期患者尿5 MedC水平明显高于早中期患者。在多元logistic回归模型中，尿5 MedC与CKD晚期的预测显著相关。当与大量白蛋白尿或尿α 1 MG水平升高（中位值，5.7 mg/gCr）联合时，尿5 MedC（中位值，65.9 μmol/gCr）能够显著预测GFR估计值下降30%或终末期肾病的发生。结论尿5 MedC水平与CKD患者肾功能损害有关，可作为预测CKD患者肾功能损害的一种新的生物标志物。进一步的研究将是必要的，以阐明尿DNA甲基化在CKD进展中的作用。
Background Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2′-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD. Method We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine α1-microglobulin (α1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner. Results The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 μmol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine α1MG (median value, 5.7 mg/gCr). Conclusion The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.