Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats
Abstract Background Although gut‐derived uremic toxins are increased in azotemic chronic kidney disease (CKD) in cats and implicated in disease progression, it remains unclear if augmented formation or retention of these toxins is associated with the development of renal azotemia. Objectives Assess...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Journal of Veterinary Internal Medicine |
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| Online Access: | https://doi.org/10.1111/jvim.17289 |
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| author | Laurens Van Mulders Ellen Vanden Broecke Ellen De Paepe Femke Mortier Lynn Vanhaecke Sylvie Daminet |
| author_facet | Laurens Van Mulders Ellen Vanden Broecke Ellen De Paepe Femke Mortier Lynn Vanhaecke Sylvie Daminet |
| author_sort | Laurens Van Mulders |
| collection | DOAJ |
| description | Abstract Background Although gut‐derived uremic toxins are increased in azotemic chronic kidney disease (CKD) in cats and implicated in disease progression, it remains unclear if augmented formation or retention of these toxins is associated with the development of renal azotemia. Objectives Assess the association between gut‐derived toxins (ie, indoxyl‐sulfate, p‐cresyl‐sulfate, and trimethylamine‐N‐oxide [TMAO]) and the onset of azotemic CKD in cats. Animals Forty‐eight client‐owned cats. Methods Nested case‐control study, comparing serum and urine gut‐derived uremic toxin abundance at 6‐month intervals between initially healthy cats that developed azotemic CKD (n = 22) and a control group (n = 26) that remained healthy, using a targeted metabolomic approach. Results Cats in the CKD group had significantly higher serum indoxyl‐sulfate (mean [SD], 1.44 [1.06] vs 0.83 [0.46]; P = .02) and TMAO (mean [SD], 1.82 [1.80] vs 1.60 [0.62]; P = .01) abundance 6 months before the detection of azotemic CKD. Furthermore, logistic regression analysis indicated that indoxyl‐sulfate (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.2‐9.0; P = .04) and TMAO (OR: 3.9; 95% CI: 1.4‐11; P = .03) were predictors for the onset of azotemia 6 months before diagnosis. However, renal function biomarkers creatinine, symmetric dimethylarginine, and urinary specific gravity were significantly correlated with indoxyl‐sulfate and TMAO abundance, causing a loss in predictive significance after correction for these factors. Conclusions Impaired gut‐derived uremic toxin handling is apparent at least 6 months before the diagnosis of azotemia, likely reflecting an already ongoing decrease in GFR, tubular function, or both. A direct causal relationship between gut‐derived uremic toxicity and the initiation of CKD in cats is still lacking. |
| format | Article |
| id | doaj-art-8e51077182d9463ca74819c9af98d072 |
| institution | Kabale University |
| issn | 0891-6640 1939-1676 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj-art-8e51077182d9463ca74819c9af98d0722025-01-27T15:22:41ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-01-01391n/an/a10.1111/jvim.17289Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in catsLaurens Van Mulders0Ellen Vanden Broecke1Ellen De Paepe2Femke Mortier3Lynn Vanhaecke4Sylvie Daminet5Faculty of Veterinary Medicine, Department of Small Animals Ghent University Merelbeke BelgiumFaculty of Veterinary Medicine, Department of Small Animals Ghent University Merelbeke BelgiumFaculty of Veterinary Medicine, Department of Translational Physiology, Infectiology and Public Health, Laboratory of Integrative Metabolomics Ghent University Merelbeke BelgiumFaculty of Veterinary Medicine, Department of Small Animals Ghent University Merelbeke BelgiumFaculty of Veterinary Medicine, Department of Translational Physiology, Infectiology and Public Health, Laboratory of Integrative Metabolomics Ghent University Merelbeke BelgiumFaculty of Veterinary Medicine, Department of Small Animals Ghent University Merelbeke BelgiumAbstract Background Although gut‐derived uremic toxins are increased in azotemic chronic kidney disease (CKD) in cats and implicated in disease progression, it remains unclear if augmented formation or retention of these toxins is associated with the development of renal azotemia. Objectives Assess the association between gut‐derived toxins (ie, indoxyl‐sulfate, p‐cresyl‐sulfate, and trimethylamine‐N‐oxide [TMAO]) and the onset of azotemic CKD in cats. Animals Forty‐eight client‐owned cats. Methods Nested case‐control study, comparing serum and urine gut‐derived uremic toxin abundance at 6‐month intervals between initially healthy cats that developed azotemic CKD (n = 22) and a control group (n = 26) that remained healthy, using a targeted metabolomic approach. Results Cats in the CKD group had significantly higher serum indoxyl‐sulfate (mean [SD], 1.44 [1.06] vs 0.83 [0.46]; P = .02) and TMAO (mean [SD], 1.82 [1.80] vs 1.60 [0.62]; P = .01) abundance 6 months before the detection of azotemic CKD. Furthermore, logistic regression analysis indicated that indoxyl‐sulfate (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.2‐9.0; P = .04) and TMAO (OR: 3.9; 95% CI: 1.4‐11; P = .03) were predictors for the onset of azotemia 6 months before diagnosis. However, renal function biomarkers creatinine, symmetric dimethylarginine, and urinary specific gravity were significantly correlated with indoxyl‐sulfate and TMAO abundance, causing a loss in predictive significance after correction for these factors. Conclusions Impaired gut‐derived uremic toxin handling is apparent at least 6 months before the diagnosis of azotemia, likely reflecting an already ongoing decrease in GFR, tubular function, or both. A direct causal relationship between gut‐derived uremic toxicity and the initiation of CKD in cats is still lacking.https://doi.org/10.1111/jvim.17289CKD developmentearly interventionfeline chronic kidney diseasepathophysiologyuremic toxicity |
| spellingShingle | Laurens Van Mulders Ellen Vanden Broecke Ellen De Paepe Femke Mortier Lynn Vanhaecke Sylvie Daminet Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats Journal of Veterinary Internal Medicine CKD development early intervention feline chronic kidney disease pathophysiology uremic toxicity |
| title | Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| title_full | Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| title_fullStr | Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| title_full_unstemmed | Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| title_short | Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| title_sort | alterations in gut derived uremic toxins before the onset of azotemic chronic kidney disease in cats |
| topic | CKD development early intervention feline chronic kidney disease pathophysiology uremic toxicity |
| url | https://doi.org/10.1111/jvim.17289 |
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