1 Department of Medicine National Taiwan University Hospital BeiHu Branch Taipei Taiwan.
2 Nephrology Division Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan.
J Am Heart Assoc. 2019 Jan 22;8(2):e010805. doi: 10.1161/JAHA.118.010805.
Background Micro RNA -125b (miR-125b) has been shown to regulate vascular calcification ( VC ), and serum miR-125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease-mineral bone disorder molecules, affect serum miR-125b levels. Methods and Results Patients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR-125b and chronic kidney disease-mineral bone disorder effectors, including intact parathyroid hormone, 25- OH -D, fibroblast growth factor-23, osteoprotegerin, and fetuin-A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR-125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR-125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR-125b levels. Osteoprotegerin ( P=0.013), fibroblast growth factor-23 ( P=0.006), and fetuin-A ( P=0.036) were linearly associated with serum miR-125b levels. High osteoprotegerin levels independently correlated with high serum miR-125 levels. Adding serum miR-125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR-125b/osteoprotegerin, with miR-125b, and both: 0.74, 0.79, and 0.81, respectively). Conclusions Serum osteoprotegerin levels ≥400 pg/mL and serum miR-125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR-125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.
Micro RNA-125b（miR-125b）已被证明可调节血管钙化（VC），血清 miR-125b 水平是估计尿毒症 VC 状态风险的潜在生物标志物。然而，目前尚不清楚临床特征，包括慢性肾脏病-矿物质和骨异常分子，是否会影响血清 miR-125b 水平。
从不同机构招募了接受慢性透析治疗≥3 个月的患者。定量检测血清 miR-125b 和慢性肾脏病-矿物质和骨异常效应物，包括完整甲状旁腺激素、25-羟维生素 D、成纤维细胞生长因子-23、骨保护素和胎球蛋白 A。我们使用多元回归分析来确定与低血清 miR-125b 水平相关的因素，并通过受试者工作特征曲线下面积确定具有密切关联的因素的最佳截断值。进一步的回归分析评估了 miR-125b 对 VC 风险的影响。在 223 名接受慢性透析治疗的患者（平均年龄 67.3 岁；平均透析时间 5.2 年）中，有 54 名（24.2%）患者血清 miR-125b 水平较高。骨保护素（P=0.013）、成纤维细胞生长因子-23（P=0.006）和胎球蛋白 A（P=0.036）与血清 miR-125b 水平呈线性相关。高骨保护素水平与高血清 miR-125b 水平独立相关。将血清 miR-125b 水平和血清骨保护素水平（≥400pg/mL）加入到估计尿毒症 VC 风险的模型中，增加了受试者工作特征曲线下面积值（对于没有 miR-125b/骨保护素、有 miR-125b 和两者的模型：0.74、0.79 和 0.81）。
血清骨保护素水平≥400pg/mL 和血清 miR-125b 水平协同增加了接受慢性透析治疗患者估计 VC 风险的准确性。在估计 VC 风险时，考虑 miR-125b 和骨保护素水平可能是合理的。
