Abstract P283: Serum Metabolites and Cardiac Death in Patients on Hemodialysis

Abstract

Introduction: Cardiovascular death is the leading cause of mortality in patients on hemodialysis. Traditional risk factors such as diabetes and hypertension do not fully account for this excess risk. Toxic metabolites that accumulate in renal failure may be responsible for accelerated cardiovascular disease, but these metabolites remain undefined. Hypothesis: The goal of this pilot study was to determine if an untargeted metabolomic approach could identify metabolites associated with cardiac death in dialysis patients. Methods: In this matched case-control study nested in the HEMO study, cases experienced cardiac death vs. were alive, respectively, at 12 months after enrollment. Cases and controls were matched on sex, race, diabetes, cardiac disease, age, and albumin. Cardiac death included death from ischemic heart disease, heart failure, and arrhythmias. Serum samples frozen at the 4 month visit were profiled by mass spectrometry. Conditional logistic regression assessed each metabolite’s association with cardiac death. Results: A total of 47 cases and 47 controls were studied. 777 metabolites available for analysis after data preprocessing. At the p<0.005 threshold, several metabolites were positively associated with cardiac death, and several metabolites were negatively associated with cardiac death. However, no metabolite had significant associations using false discovery rate thresholds. Conclusions: Our study is an example of the use of metabolomics as a strategy for identification of metabolites that may explain the high risk of cardiac death in patients undergoing hemodialysis. Figure 1: Odds ratio for 1-year risk of cardiac death per doubling of metabolite level for each metabolite in the HEMO Study