Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Dis Markers. 2019 Jul 1;2019:5432453. doi: 10.1155/2019/5432453. eCollection 2019.
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.
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 1-microglobulin (1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner.
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 mol/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 1MG (median value, 5.7 mg/gCr).
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.
DNA 甲基化的改变可能与慢性肾脏病（CKD）患者的疾病进展有关。最近的研究表明，5-甲基-2'-脱氧胞苷（5MedC）可能是 DNA 过度甲基化的标志物。目前，尚无关于 5MedC 尿液水平及其与 CKD 进展之间关系的信息。
我们使用竞争性酶联免疫吸附试验检测了 308 例 CKD 患者（中位年龄：56 岁，男性：53.2％，肾小球肾炎：51.0％）的晨尿样本中的 5MedC 尿液水平，并研究了 5MedC 与 CKD 相关的实验室参数之间的关系。前瞻性地对患者进行了 3 年的随访，以评估肾脏终点。
与 CKD 的早期到中期相比，CKD 的晚期尿液 5MedC 水平显着增加。在多元逻辑回归模型中，尿液 5MedC 与预测较晚的 CKD 阶段显着相关。尿液 5MedC（中位数，65.9 mol/gCr）与宏白蛋白尿或尿液 1MG 水平升高相结合（中位数，5.7 mg/gCr），显着能够预测 eGFR 下降 30％或终末期肾病的发生。
本研究数据表明，尿液 5MedC 水平与肾功能降低有关，可作为预测 CKD 患者肾脏结局的新型有效生物标志物。需要进一步的研究来阐明尿液 DNA 甲基化在 CKD 进展中的作用。
