Beyond waste: arginine metabolism and ammonium detoxification in cardiovascular-renal-metabolic disease.

Ammonium is a toxic product of amino acid degradation and protein turnover that is incorporated into arginine and detoxified via the urea cycle. Recent work has expanded the role of ammonium detoxification and the urea cycle toward broader metabolic functions. This review examines how ammonium and urea cycle-related metabolites function beyond nitrogen disposal and work as bioactive regulators across the cardiovascular, renal, and metabolic disease spectrum. We discuss how interorgan coordination among the gut, liver, kidney, heart, and immune system links arginine metabolism, ammonium detoxification, and metabolic signaling. Evidence suggests that ammonium can influence mitochondrial function, inflammatory tone, and tissue remodeling. The review considers how noncanonical urea cycle activity may contribute to chronic kidney disease, heart failure, and metabolic dysfunction.