Metabolite Biomarkers of CKD Progression in Children.

Link: https://doi.org/10.2215/CJN.00220121
Authors: Denburg, Michelle R; Xu, Yunwen; Abraham, Alison G; Coresh, Josef; Chen, Jingsha; Grams, Morgan E; Feldman, Harold I; Kimmel, Paul L; Rebholz, Casey M; Rhee, Eugene P; Vasan, Ramachandran S; Warady, Bradley A; Furth, Susan L; ,

Abstract: Metabolomics facilitates the discovery of biomarkers and potential therapeutic targets for CKD progression. We evaluated an untargeted metabolomics quantification of stored plasma samples from 645 Chronic Kidney Disease in Children (CKiD) participants. Metabolites were standardized and logarithmically transformed. Cox proportional hazards regression examined the association between 825 nondrug metabolites and progression to the composite outcome of KRT or 50% reduction of eGFR, adjusting for age, sex, race, body mass index, hypertension, glomerular versus nonglomerular diagnosis, proteinuria, and baseline eGFR. Stratified analyses were performed within subgroups of glomerular/nonglomerular diagnosis and baseline eGFR. Untargeted plasma metabolomic profiling facilitated discovery of novel metabolite associations with CKD progression in children that were independent of established clinical predictors and highlight the role of select biologic pathways.