Candidate urinary biomarkers show promise for distinguishing between calcium oxalate versus struvite urolithiasis in dogs

Abstract

Abstract OBJECTIVE To identify metabolites and metabolic pathways affected in dogs with struvite and calcium oxalate urolithiasis compared to healthy dogs. To explore the candidate urinary biomarkers to distinguish dogs with struvite and calcium oxalate urolithiasis. ANIMALS 13 dogs with calcium oxalate urolithiasis, 7 dogs with struvite urolithiasis, and 13 healthy dogs were recruited between September 2021 and January 2023. METHODS Metabolomic profiles were analyzed from urine samples using UPLC-MS MS. According to the variable importance in the projection (> 1) and correlation coefficient (P < .05) obtained by orthogonal partial least squares discriminant analysis, the differential metabolites were screened. The Kyoto Encyclopedia of Genes and Genomes database was used to identify the metabolic pathways involved. RESULTS Compared to healthy dogs, those with calcium oxalate urolithiasis exhibited distinct metabolites primarily associated with phenylalanine metabolism, nicotinic acid, and nicotinamide metabolic pathways. Conversely, dogs with struvite urolithiasis demonstrated variations in metabolites mainly linked to tryptophan metabolism and glycerophospholipid metabolic pathways. Between calcium oxalate and struvite groups, pyocyanin, glycylprolylarginine, traumatin, cysteinyl-leucine, and 8-hydroxydodecylcarnitine are candidate urinary biomarkers. CLINICAL RELEVANCE Our findings provide an in-depth analysis of metabolic perturbations associated with calcium oxalate and struvite urolithiasis in dogs. We also identified candidate urinary biomarkers distinguishing between dogs with calcium oxalate and struvite urolithiasis, which can be subsequently validated to assist in stone diagnosis and guide treatment choices.