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.
17 - 20 May 2014
European Calcified Tissue Society