Background: Microbial metabolites of the amino acid phenylalanine are emerging as biomarkers of dysregulated gut microbial metabolism in cats with chronic kidney disease (CKD), but many of these metabolites have not yet been quantified in this population.
Objective: Determine serum concentrations of phenylalanine-derived metabolites in cats with CKD and healthy cats. Animals: 112 client-owned adult cats (healthy, n = 66; CKD Stages 1-4, n = 46).
Methods: Retrospective cross-sectional study. Quantitative liquid chromatography-mass spectrometry was used to measure serum concentrations phenylalanine and its microbial-derived metabolites. Metabolite concentrations were compared between healthy and CKD cats using Wilcoxon rank-sum tests and between healthy cats and disease severity (healthy vs Stage 1-2 CKD vs Stage 3-4 CKD) using Kruskal-Wallis tests.
Results: Cats with CKD had a lower median serum phenylalanine concentration compared to healthy cats (38.4 [range, 25.0-124.2 mcg/mL] vs. 46.5 [23.0-83.2 mcg/ml] ; P = 0.023). For microbial-derived metabolites, cats with CKD had higher median phenylacetylglutamine (79 [9-422 ng/mL] vs. 28 [4-291 ng/mL]; P < 0.001) and phenylacetylglycine (6,291 [432-34,234 ng/mL] vs. 2,168 [327-12,286 ng/mL]; P < 0.001) concentrations and lower median phenyllactic acid (159 [58-722 ng/mL] vs. 279 [91-985 ng/mL]; P < 0.001) concentration compared to healthy cats. Concentrations of phenylalanine-derived metabolites correlated with disease severity, peaking in cats with Stages 3-4 (P < 0.05). Conclusions and Clinical Importance: CKD is associated with altered microbial metabolism of phenylalanine leading to accumulation of gut-derived uremic toxins and depletion of phenyllactic acid. These metabolites are novel biomarkers and targets for microbiome-modulating therapies.
