Journal of veterinary internal medicine · 2025
Metabolic Alterations Associated With Rapidly Progressive Chronic Kidney Disease in Cats.
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van Mulders Laurens, Vanden Broecke Ellen, Mortier Femke, de Paepe Ellen, Vanhaecke Lynn, Daminet Sylvie
Аннотация
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 = 8) and a non-progressive control group (n = 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 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 < 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).
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.
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 = 8) and a non-progressive control group (n = 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 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 < 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).
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.