Abstract MP11: Serum Metabolites Associate With Kidney Function Among Bogalusa Heart Study Participants

Abstract

Chronic kidney disease (CKD) is an important public health challenge due to its high prevalence, potential for progression to end-stage renal disease, and associated increases in risks of cardiovascular disease morbidity and mortality. While traditional risk factors for reduced kidney function have been identified, the biological pathways underlying this complex phenotype remain largely unknown. A metabolome-wide association study was conducted among 825 white and 436 African-American participants of the Bogalusa Heart Study (BHS) to identify metabolites associated with kidney function. Estimated glomerular filtration rate (eGFR) was calculated among BHS participants using the CKD Epidemiology Collaboration (CKD-EPI) equation. Untargeted, ultra-high performance liquid chromatography tandem-mass spectroscopy was used to quantify 1,466 metabolites. A total of 1,202 metabolites passing rigorous quality control were tested for association with eGFR in race stratified and combined multiple regression analyses that adjusted for age, sex, education, cigarette smoking, alcohol drinking, physical activity, body mass index, and race (in combined analyses). Significant metabolites were identified as those achieving Bonferroni corrected significance (P<4.16х10 -5 ) in one race group and the entire cohort, with a similar trend observed in the other race group. Results of these analyses are presented in the Figure . Among 302 significant metabolites, 89 were novel and in known metabolic pathways, 106 were novel and in unknown metabolic pathways, and 107 were previously reported. The 89 novel metabolites were classified into the following pathways: 40 in amino acids, 3 in carbohydrates, 7 in cofactors, 1 in energy, 6 in nucleotides, 9 in peptides, and 14 in xenobiotics. In conclusion, the current analysis not only validated previous findings, but identified novel metabolites associated with kidney function. These data provide important insights into the biological pathways underlying this complex phenotype.