Preventing vascular calcification in kidney disease

Project Summary: Title: Preventing vascular calcification in kidney disease. Chronic kidney disease (CKD) affects roughly 9-10% of the world’s population and contributes directly to over one million deaths annually. Mortality risk and morbidity in young CKD and dialysis patients correlates strongly with vascular calcification severity (VC). The precise processes responsible for the build-up of mineral remain unknown. Recent research has highlighted the likely role of calciprotein particles (CPPs) in initiation and progression of VC. Calciprotein particles are small colloidal nanoparticles found in the circulation that induce the calcification and osteogenic transformation of vascular smooth muscle cells. Secondary crystalline calciprotein particles (CCP2) that transform from primary amorphous particles (CPP1) play a major role in the VC process. Importantly, as renal disease progresses a suppression of factors inhibiting CPP2 genesis occurs. Our preliminary studies show reduced serum levels of a candidate factor “ASARM peptide” in CKD rodents and patients with end-stage kidney disease. Importantly, CKD rodent models treated with synthetic ASARM peptide have major and significant suppression of VC with improved renal function. We hypothesize ASARM peptide(s) could play a significant role in the etiology of vascular calcification by interacting with CPPs. This study will determine the utility of synthetic ASARM-peptide for preventing VC and the mechanisms involved. Also we will determine whether abnormal expression or processing of circulating ASARM peptides occurs in patients with CKD and determine if ASARM levels predict calcification propensity or associate with markers of calcification risk.