Serum and urine metabolomic profiling in Miniature Schnauzer dogs with and without calcium oxalate urolithiasis.

Abstract

INTRODUCTION: Calcium oxalate (CaOx) urolithiasis is associated with metabolic disorders, including dyslipidemia. Improved understanding of underlying metabolic derangements is needed. The Miniature Schnauzer presents an opportunity to investigate connections between hyperlipidemia and CaOx stones, as both are prevalent in the breed. OBJECTIVES: To characterize lipidomic (serum) and metabolomic (serum and urine) profiles in Miniature Schnauzers with (cases) and without (controls) CaOx urolithiasis. METHODS: Ultrahigh performance liquid chromatography-tandem mass spectroscopy was performed on serum from cases (n = 15) and controls (n = 27) for lipidomic and metabolomic analysis. Urine metabolomics was included for a subset of dogs. Ten metabolites with previously established biological links to urolithiasis were prespecified as "high priority." Cases and controls were compared to identify differentially abundant metabolites (FDR-adjusted q-values). RESULTS: No lipid species were differentially abundant. Three serum metabolites differed between groups (all lower in cases): 10-undecenoate, N-delta-acetylornithine, and glutarate (q-values 0.005, 0.03, and 0.009, respectively). Cluster analysis of high priority metabolites identified a subset of cases with distinct profiles, characterized by lower citrate and higher phosphate, glycine, and hippurate. Urinary profiles exhibited 202 differentially abundant metabolites, including higher acetylcarnitine and carnitine in cases (q-values 0.002 for both). CONCLUSIONS: No differences in lipids were identified between Miniature Schnauzers with and without CaOx stones. Distinct metabolic subsets of stone formers might exist within the breed. Reduced N-delta-acetylornithine in stone formers is also reported in human stone formers and might reflect dietary acid load. Acetylcarnitine and carnitine enrichment in the urine of stone formers also warrants further exploration.