Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review
Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being d...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13197 |
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| author | Sabbir Ahmed Joost C. de Vries Jingyi Lu Milan H. Verrijn Stuart Silvia M. Mihăilă Robin W. M. Vernooij Rosalinde Masereeuw Karin G. F. Gerritsen |
| author_facet | Sabbir Ahmed Joost C. de Vries Jingyi Lu Milan H. Verrijn Stuart Silvia M. Mihăilă Robin W. M. Vernooij Rosalinde Masereeuw Karin G. F. Gerritsen |
| author_sort | Sabbir Ahmed |
| collection | DOAJ |
| description | Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (<i>n</i> = 41), mice (<i>n</i> = 17), dogs (<i>n</i> = 3), cats (<i>n</i> = 4), goats (<i>n</i> = 1), and pigs (<i>n</i> = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans. |
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| id | doaj.art-f5e232913d884b3fae8ab1d62e2ab698 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:22:02Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f5e232913d884b3fae8ab1d62e2ab6982023-11-19T08:13:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171319710.3390/ijms241713197Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic ReviewSabbir Ahmed0Joost C. de Vries1Jingyi Lu2Milan H. Verrijn Stuart3Silvia M. Mihăilă4Robin W. M. Vernooij5Rosalinde Masereeuw6Karin G. F. Gerritsen7Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsProtein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (<i>n</i> = 41), mice (<i>n</i> = 17), dogs (<i>n</i> = 3), cats (<i>n</i> = 4), goats (<i>n</i> = 1), and pigs (<i>n</i> = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans.https://www.mdpi.com/1422-0067/24/17/13197chronic kidney diseaseprotein-bound uremic toxinsanimal modelsindoxyl sulfatehippuric acidpara-cresyl sulfate |
| spellingShingle | Sabbir Ahmed Joost C. de Vries Jingyi Lu Milan H. Verrijn Stuart Silvia M. Mihăilă Robin W. M. Vernooij Rosalinde Masereeuw Karin G. F. Gerritsen Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review International Journal of Molecular Sciences chronic kidney disease protein-bound uremic toxins animal models indoxyl sulfate hippuric acid para-cresyl sulfate |
| title | Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review |
| title_full | Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review |
| title_fullStr | Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review |
| title_full_unstemmed | Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review |
| title_short | Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review |
| title_sort | animal models for studying protein bound uremic toxin removal a systematic review |
| topic | chronic kidney disease protein-bound uremic toxins animal models indoxyl sulfate hippuric acid para-cresyl sulfate |
| url | https://www.mdpi.com/1422-0067/24/17/13197 |
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