Metabolic Alterations Associated With Rapidly Progressive Chronic Kidney Disease in Cats.

Abstract

BACKGROUND: Chronic kidney disease (CKD) in cats often remains stable over time, but some cats experience progressive kidney dysfunction without an identifiable cause. OBJECTIVES: Identify differences in serum and urine compounds related to tryptophan metabolism and gut-derived uremic toxins between cohorts with non-progressive and rapidly progressive CKD. ANIMALS: Forty-two client-owned cats diagnosed with CKD were divided into a rapid progression group (n&#x2009;=&#x2009;8) and a non-progressive control group (n&#x2009;=&#x2009;34). METHODS: Prospective cohort study with comparative analysis of predictors using targeted metabolomics. Rapid progression was defined as a 25% increase in serum creatinine concentration over 6&#x2009;months. RESULTS: Serum metabolite ratios of the serotonin pathway showed promising potential for predicting rapid CKD progression in cats: L-tryptophan/5-hydroxytryptophan (area under curve [AUC]: 0.89; 95% CI: 0.78-1; p&#x2009;<&#x2009;0.01; sensitivity: 85.7%; specificity: 78.8%) and serotonin/5-hydroxyindole-3-acetic acid (AUC: 0.83; 95% CI: 0.64-1; p&#x2009;<&#x2009;0.01; sensitivity: 87.5%; specificity: 76.5%). Cats with rapidly progressive CKD had significantly lower baseline urinary indoxyl-sulfate (median [Interquartile range, IQR], 0.25 [0.07-0.46] vs. 0.53 [0.36-0.81]; p&#x2009;=&#x2009;0.04) and p-cresyl-sulfate (median [IQR], 0.13 [0.01-0.79] vs. 0.83 [0.32-1.27]; p&#x2009;=&#x2009;0.04). Logistic regression analysis identified an association between decreased urinary indoxyl-sulfate (odds ratio [OR]: 0.03; 95% CI: 0-1; p&#x2009;=&#x2009;0.04) and rapidly progressive CKD, following a similar pattern after correcting for serum creatinine concentration (p&#x2009;=&#x2009;0.06). CONCLUSIONS: Metabolites of the serotonin pathway: L-tryptophan, 5-hydroxytryptophan, and 5-hydroxyindole-3-acetic acid may serve as potential candidates for further predictive validation in CKD progression in cats. Decreased uremic toxin excretion in rapidly progressive CKD may underlie disease progression.