Risk factors associated with altered circulating microRNA-125B and their influences on uremic vascular calcification among patients with end-stage renal disease
Journal
Journal of the American Heart Association
Journal Volume
8
Journal Issue
2
Pages
e010805
Date Issued
2019
Author(s)
Abstract
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 mi R?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 VCincreased 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. ? 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
SDGs
Other Subjects
calcifediol; circulating microRNA; fetuin A; fibroblast growth factor 23; microRNA 125b; osteoprotegerin; parathyroid hormone; biological marker; microRNA; MIRN125 microRNA, human; osteoprotegerin; aged; Article; blood vessel calcification; bone disease; cohort analysis; correlational study; disease association; end stage renal disease; female; hemodialysis; human; major clinical study; male; multicenter study; parathyroid hormone blood level; priority journal; protein blood level; risk factor; vitamin blood level; blood; blood vessel calcification; chronic kidney failure; clinical trial; complication; enzyme linked immunosorbent assay; follow up; prospective study; radiography; radioimmunoassay; risk factor; uremia; Aged; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; MicroRNAs; Osteoprotegerin; Prospective Studies; Radiography; Radioimmunoassay; Renal Dialysis; Risk Factors; Uremia; Vascular Calcification
Publisher
American Heart Association Inc.
Type
journal article