Our disease enrichment analysis (Figure 5B) revealed metabolites (categories I and II) related to creatine deficiency and hemodialysis along with methionine adenosyl transferase, hyperpipecolatemia, and ornithine transcarbamylase deficiency, which depend on kidney clearance, and compounds linked to ESKD complications such as inflammation, diabetes (energy metabolism disturbance), and early markers on myocardial injury (presumably due to a larger blood volume that increases the heart workload in CKD) (Aoki and Ikari, 2017). This evidence concerns the gene OTC and chronic kidney disease.