Risk Factors Associated With Altered Circulating MicroRNA-125b and Their Influences on Uremic Vascular Calcification Among Patients With End-Stage Renal Disease

Background MicroRNA-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.