Background: The gut-kidney axis plays a direct role in gastrointestinal and kidney health. Gut-derived metabolites like uremic toxins are associated with the physiopathogenesis of feline chronic kidney disease (CKD).
Objectives: Identify novel fecal biomarkers and roles of gastrointestinal metabolites in feline CKD. Animals: Forty-one healthy non-CKD (control) and 67 CKD cats, including 5 IRIS stage 1 (CKD1), 37 stage 2a (CKD2a), 18 stage 2b (CKD2b), and 7 stage 3 (CKD3).
Results: Statistical analysis identified 64 differential metabolites between control and various stages of CKD (P < 0.001). More than 60% of the metabolites were lipids, including polyunsaturated long-chain fatty acids, acylcarnitines, and ceramides. Random Forest algorithm selected N1-methyl-2-pyridone-5-carboxamide (2PY), a uremic toxin from nicotinamide catabolism, as the top fecal marker for classifying feline CKD. 2PY was increased in CKD1 (P = 0.03), CKD2a, CKD2b, and CKD3 (all P < 0.0001) compared to the control. Data mining revealed serum concentration of 2PY was significantly increased with the severity of CKD in cats, possibly due to impaired renal excretion. Cholesterol and arachidonate, markers for enterocyte membrane shedding and inflammation, were increased in CKD3 versus control (both P < 0.05). Finally, branched chain fatty acid isobutyrate and isovalerate were increased in CKD versus control (all P < 0.05). Conclusions and Clinical Importance: The study revealed 2PY as a novel marker and unveiled profound alterations in gastrointestinal lipid compositions with a potential link to gut barrier integrity and inflammation in CKD.
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.jpg "Qinghong Li, PhD photo")