Abstract
Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development.
Highlights
Chronic kidney disease (CKD) is a public health condition, affecting 13% to25% of the worldwide population. [1, 2]
The aim of the present study was to identify the role of miRNAs in end-stage renal disease (ESRD) patients with CKD-Mineral and bone disorder (MBD) and to elucidate possible links between miRNAs and the traditional bone turnover serum marker parathyroid hormone (PTH)
We identified miRNAs associated with PTH level which can reference adynamic bone disease (ABD) in ESRD patients
Summary
Chronic kidney disease (CKD) is a public health condition, affecting 13% to25% of the worldwide population. [1, 2]. In addition to SHPT, the prevalence of adynamic bone disease (ABD) is not negligible in CKD patients and is observed in 10% to 71% of patients in CKD stage 5D [6,7,8,9] These bone remodeling problems result in a higher prevalence of hip fracture in CKD patients than in the healthy population [10,11,12,13,14,15,16], hip fracture in CKD stages 3–5 patients with is associated with a mortality rate twice that in non-dialysis patients with a hip fracture [12, 17]. Coronary artery calcification is one of the primary causes of cardiovascular-related death in patients on dialysis as it can lead to cardiac ischemia and sudden death [18,19,20]
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