ECTS Abstracts (2015) 1 P406

Specific MicroRNAs as Biomarkers in CKD Patients at High Risk for Calcifications and ROD?

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

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

Background: Calcification of vessels, mainly in the tunica media, with concomitant demineralisation of bone is typical for patients suffering from chronic kidney disease (CKD). In this project, we analyse samples from CKD patients with a focus on microRNAs (miRNAs) as new biomarkers for vascular calcification. Our aim is to find a pattern of miRNAs indicating vascular calcification and/or mineralisation changes in the course of the disease.

Methods: Serum and plasma samples of 73 patients in CKD stages 3 – 5, 67 post RT (renal transplantation) patients as well as 36 healthy controls are analysed in the study. Additional 25 patients in CKD stage 5 were prospectively followed before, and already some of them during and after RT. Known biomarkers for calcification have been measured using ELISA techniques. A miRNA profile of CKD patients compared to healthy controls has been established using an nCounter® miRNA Expression Assay. Deregulated miRNAs were further analysed in qPCR experiments.

Results: PTH, FGF23 and osteocalcin were significantly increased in late stage CKD patients. When analysing more than 800 miRNAs, a significant difference was found in 37 when comparing CKD patients of stage 5 and healthy controls. Those miRNAs were connected to vascular smooth muscle cell (VSMC) biology and bone metabolism, especially miR-146a, miR-145 and miR-223, which showed an up to 13-fold expression difference during qPCR experiments.

Discussion: MiRNAs with a biological association to vascular calcification, bone metabolism or differentiation of VSMCs to osteoblast-like cells are deregulated to a considerable amount in CKD patients. These pathways may be important during the development of calcified tissue in the course of kidney disease. MiRNA profiles could be early diagnostic markers indicating the risk of vascular calcification or bone demineralisation in this high risk group.

Disclosure: The authors declared no competing interests. This work was supported by the Austrian National Bank Anniversary Fund (OeNB 15635) and the Austrian Science Fund (FWF).