Background Intestinal dysbiosis has been documented in humans with chronic kidney disease (CKD) and is thought to contribute to production of the uremic toxins indoxyl sulfate (IS) and p‐cresol sulfate (pCS). Characteristics of the fecal microbiome in cats with CKD and correlation to serum concentrations of uremic toxins are unknown. Objectives To characterize the fecal microbiome and measure serum IS and pCS concentrations of cats with CKD in comparison to healthy older cats. Animals Thirty client‐owned cats with CKD (International Renal Interest Society stages 2‐4) and 11 older (≥8 years) healthy control cats. Methods Prospective, cross‐sectional study. Fecal samples were analyzed by sequencing of 16S rRNA genes and Escherichia coli quantitative PCR (qPCR). Serum concentrations of IS and pCS measured using liquid chromatography tandem mass spectrometry. Results Cats with CKD had significantly decreased fecal bacterial diversity and richness. Escherichia coli qPCR showed no significant difference in bacteria count between control and CKD cats. Cats with stage 2 (P = .01) and stages 3 and 4 (P = .0006) CKD had significantly higher serum IS concentrations compared to control cats. No significant difference found between stage 2 and stages 3 and 4 CKD. The pCS concentrations were not significantly different between CKD cats and control cats. Conclusions and Clinical Importance Decreased fecal microbiome diversity and richness is associated with CKD in cats. Indoxyl sulfate concentration is significantly increased with CKD, and cats with stage 2 CKD may suffer from a similar uremic toxin burden as do cats with later stage disease.

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs.

Background High dietary phosphorus (P) and low calcium‐to‐phosphorus ratio (Ca:P) are associated with kidney damage in cats. There are no established guidelines for dietary P maximum for cats. Objectives To quantify crude protein, P, Ca, and magnesium (Mg) concentrations in cat foods and compare among food formats (dry, canned, raw), primary protein ingredients, protein concentrations (low, moderate, high), grain‐free versus grain‐containing foods, foods intended for adult maintenance versus all life stages, and cost. Samples Eighty‐two commercial nonprescription cat foods. Methods Descriptive study. Mineral concentrations were measured using inductively coupled argon plasma‐optical emission spectroscopy. Crude protein was measured using the Dumas nitrogen combustion method. Mineral and crude protein concentrations were compared among food categories. Results Twenty‐seven foods contained ≥3.6 g P/1000 kcal metabolizable energy (ME), of which 7 exceeded 4.8 g/1000 kcal ME. Thirteen foods had low Ca:P ratio (≤1.0). The low‐protein diet group had no products ≥3.6 g P/1000 kcal ME, which was significantly different compared to the high‐protein diet group (52% of products had ≥3.6 g P/1000 kcal ME; P = .01). No significant differences in P content and Ca:P ratio were found among other diet categories. Canned foods had significantly lower Mg compared to dry (P < .001) and raw (P = .007) foods. Declared minimum P and Ca were significantly lower than analyzed concentrations (P = .0005 and P = .003, respectively). Conclusions and Clinical Importance The high number of foods with high P and low Ca suggest that pet food regulatory reform should be considered.

Background Straight‐ and branched‐chain (BCFA) short‐chain fatty acids (SCFAs) are produced by colonic microbiota and have both beneficial and deleterious effects in humans with chronic kidney disease (CKD). Fecal SCFAs in cats with CKD have not been described. Objective To characterize fecal SCFA concentrations in cats with CKD as compared to healthy geriatric cats and correlate SCFA to serum indoxyl sulfate (IS) and p‐cresol sulfate (pCS) concentrations. Animals Twenty‐eight cats with CKD (International Renal Interest Society [IRIS] stages 2, 3, and 4) and 11 older (≥ 8 years) healthy geriatric cats. Methods Prospective, cross‐sectional study. Voided feces were analyzed using stable isotope dilution gas chromatography‐mass spectrometry to determine fecal concentrations of SCFAs. Serum concentrations of IS and pCS were measured using liquid chromatography tandem mass spectrometry. Results Fecal isovaleric acid concentrations were significantly higher in CKD cats(P = .02) Cats with IRIS CKD stage 3 and 4 had significantly higher fecal isovaleric acid concentrations compared to healthy geriatric cats (P = .03), but not compared to IRIS CKD stage 2 cats. Total fecal concentrations of BCFAs were found to correlate weakly with serum creatinine concentration (rho, 0.33; P = .05), blood urea nitrogen concentration (rho, 0.40; P = .01), and pCS concentration (rho, 0.35; P = .04). Conclusions and Clinical Importance Fecal isovaleric acid concentrations were higher in CKD cats, particularly in late stage disease, compared to healthy geriatric cats. Fecal BCFA concentrations correlated with pCS and were higher in cats with muscle wasting, providing evidence for malassimilation of protein in CKD cats.

Chronic kidney disease (CKD) in cats and dogs presents significant clinical challenges, with emerging research highlighting the pivotal role of the gut-kidney axis in its pathogenesis and management. Gut dysbiosis, characterized by alterations in the gut microbiome composition and function, contributes to microbial dysmetabolism of key nutrients causing uremic toxin accumulation and disruptions in amino acid, bile acid and fatty acid profiles. These disturbances in turn exacerbate renal dysfunction and systemic inflammation. Recent research in veterinary medicine, particularly in cats, supports the gut microbiome and microbial-derived metabolites as novel therapeutic targets. Potential therapeutic strategies targeting the gut microbiome and microbial dysmetabolism, including dietary management, probiotics, adsorbents, and addressing constipation, offer promising avenues for intervention to restore metabolic balance and preserve renal function. This review highlights the microbial influence on renal health and focuses on potential therapeutic strategies available to veterinarians to optimize the management of CKD in cats and dogs.