Coronary calcification in hemodialysis patients

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DESCRIPTION (provided by applicant): Patients with chronic kidney disease (CKD) have an increased mortality rate and cardiovascular disease (CVD) accounts for approximately 50% of deaths in these patients. It is an atypical form of atherosclerosis with increased deposition of calcium in the atherosclerotic plaque, thickening of the media and not fully explained by traditional risk factors. Vascular calcification (VC) which leads to arterial stiffness and left ventricular hypertrophy is likely to be a major contributant to the pathology. Recent evidence suggest that a chronic inflammatory state and alterations of bone mineral metabolism and circulating VC inhibitors which are common in dialysis patients may play an important role in the vascular calcification process. We are responding to PA-06-148 Pilot and Feasibility Program Related to the Kidney whose objective is to use epidemiological and biochemical approaches to identify new, non-traditional risk factors for CVD in patients with CKD. Coronary artery calcification (CAC) is common in this population and has been associated with increased mortality. Pulse wave velocity has also been found to be independently associated with mortality in this patients. These two non-invasive measurements will be able to provide an assessment of the degree of vascular calcification and compliance in each subject. We hypothesize that in individuals with the highest levels of inflammatory and alteration of bone metabolism, CAC will be more prevalent and progress more rapidly in a 12-month period than in those with normal inflammatory state and bone metabolism. We propose to enroll a cohort of 125 incident asymptomatic dialysis patients and obtain measurements of CAC and PWV prospectively. Our main tool for analysis will be Wilcoxon rank-sum test and standard mixed effects growth curve models. The study findings will aid in identifying risk factors whose risk profile we can alter in future randomized clinical trials. In addition, it will provide insight on whether current clinical therapies are increasing the burden of calcification in our dialysis population.