<p><strong>BACKGROUND: </strong>Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease.</p><p><strong>METHODS: </strong>We used data from 3736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin-to-creatinine ratio (UACR). Metabolites were quantified in fasting serum through nontargeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites, in covariate-adjusted models that accounted for the study design. In total, 132 metabolites were available for replication in the Hypertension Genetic Epidemiology Network study ( n =300), and 29 metabolites were available for replication in the Malmö Offspring Study ( n =999).</p><p><strong>RESULTS: </strong>Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-glutamine and D-glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism.</p><p><strong>CONCLUSIONS: </strong>Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanic/Latino population.</p><p><strong>PODCAST: </strong>This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/C…;