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

J Am Heart Assoc. 2019 Jan 22;8(2):e010805. doi: 10.1161/JAHA.118.010805.

Abstract

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.

Keywords: biomarker; chronic kidney disease; end‐stage renal disease; fibroblast growth factor‐23; microRNA‐125b; osteoprotegerin; vascular calcification.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Male
  • MicroRNAs / blood*
  • Osteoprotegerin / blood
  • Prospective Studies
  • Radiography
  • Radioimmunoassay
  • Renal Dialysis
  • Risk Factors
  • Uremia / blood
  • Uremia / complications*
  • Uremia / therapy
  • Vascular Calcification / blood*
  • Vascular Calcification / diagnosis
  • Vascular Calcification / etiology

Substances

  • Biomarkers
  • MIRN125 microRNA, human
  • MicroRNAs
  • Osteoprotegerin