Bone Abstracts (2014) 3 PP383 | DOI: 10.1530/boneabs.3.PP383

MicroRNAs as new biomarkers for monitoring of vascular calcification in CKD patients

Matthias Ulbing1, Natascha Schweighofer1, Bettina Leber3, Sandra Lemesch4, Alexander Rosenkranz2, Kathrin Eller2, Alexander Kirsch2, Helmut Müller3, Vanessa Stadlbauer4 & Barbara Obermayer-Pietsch1

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria; 2Division of Nephrology, Department of Internal Medicine, Medical University Graz, Graz, Austria; 3Division of Transplant Surgery, Department of Surgery, Medical University Graz, Graz, Austria; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Graz, Austria.

Introduction: Calcification of vessels, especially media calcification, in combination with bone demineralization and disturbed bone metabolism is abundant in patients suffering from end stage renal disease (ESRD). In this project, we compare biomarkers of calcification with a focus on microRNAs from ESRD patients listed for renal transplantation (RTX) and healthy controls.

Methods: Samples are collected from kidney transplant patients. At the same time this patients are examined clinically to establish the degree of calcification. Systemic biomarkers as indicators of calcification mechanisms are analyzed with a focus on micoRNAs, new important regulators of gene expression. Clinical characterization including documentation of the vessel calcification status, go along with analysis of biomarkers of bone metabolism. MicroRNA profiles are measured in serum using the nCounter analysis system (Nanostring) and qPCR.

Results: Several regulators important for mineralization, such as FGF23, PTH, TRAP or bALP, show different levels comparing healthy controls and ESRD patients.

Further microRNAs have been isolated from serum of ESRD patients and controls and the presence of U6snRNA as well as hsr-miR23a has been checked as a control. 15 samples from patients with a glomerular filtration rate <20 and nine healthy controls have been used for the profiling with the Nanostring-Technology, evaluating the concentration of 800 different microRNAs. Differentially expressed microRNAs are further tested by qPCR.

Conclusion: MicroRNAs playing a role during vascular calcification and osteoblast-like differentiation of VSMCs are identified in samples from ESRD patients. They are potential new biomarkers for cardiovascular and osteological complications. Specific microRNA profiles from ESRD patients may be early diagnostic markers indicating the risk for vascular calcification and demineralization of bone, and serve as putative targets for therapy options in the future.