Metabolic Alterations Associated With Rapidly Progressive Chronic Kidney Disease in Cats

Chronic kidney disease (CKD) in cats often remains stable over time, but some cats experience progressive kidney dysfunction without an identifiable cause.

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.

Forty-two client-owned cats diagnosed with CKD were divided into a rapid progression group (n = 8) and a non-progressive control group (n = 34).

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 months.

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 < 0.01; sensitivity: 85.7%; specificity: 78.8%) and serotonin/5-hydroxyindole-3-acetic acid (AUC: 0.83; 95% CI: 0.64-1; p < 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 = 0.04) and p-cresyl-sulfate (median [IQR], 0.13 [0.01-0.79] vs. 0.83 [0.32-1.27]; p = 0.04). Logistic regression analysis identified an association between decreased urinary indoxyl-sulfate (odds ratio [OR]: 0.03; 95% CI: 0-1; p = 0.04) and rapidly progressive CKD, following a similar pattern after correcting for serum creatinine concentration (p = 0.06).

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.