Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins
Abstract
:1. Introduction
2. Gut-Derived Uremic Toxins
2.1. Trimethylamine-N-Oxide
2.2. Indoxyl Sulfate
2.3. Indole Acetic Acid
2.4. P-Cresyl Sulfate
2.5. Nonpharmacological Interventions, Dietary Changes, and Uremic Toxin Concentrations
3. Phosphate Binders
3.1. Calcium-Based Phosphate Binders
3.2. Magnesium-Based Phosphate Binders.
3.3. Calcium-Free/Noncalcium-Based Phosphate Binders
3.4. Iron-Based Phosphate Binders
4. Phosphate Binders and Gut-Derived Uremic Toxins
4.1. Phosphate Binders and the Gut Microflora
4.2. Phosphate Binders and Gut-Derived Uremic Toxins
4.2.1. Experimental Data
4.2.2. Observational Studies
4.2.3. Interventional Studies
5. Sorbents and Uremic Toxins
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Calcium-Based Phosphate Binders | Magnesium/Calcium-Based Phosphate Binders | Calcium-Free Phosphate Binders | ||||
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Calcium carbonate Calcium acetate | Magnesium carbonate | Sevelamer | Lanthanum carbonate | Iron-Based Phosphate Binders | ||
Ferric citrate | Sucroferric oxyhydroxide | |||||
Advantages |
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Disadvantages |
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In Vitro Studies | |||||
First Author Year | Type of Binder | Type of Gut-Derived Uremic Toxin | Results | ||
De Smet R. 2016 (abstract) [77] | Sevelamer hydrochloride | IAA, p-cresol, indole | Sevelamer hydrochloride was able to adsorb indole, IAA and p-cresol | ||
Bennis Y. 2019 [78] | Sevelamer carbonate | IAA, p-cresol, indole | Sevelamer carbonate was able to adsorb IAA but not indole or p-cresol | ||
Animal Studies | |||||
First Author Year | Type of Models | Type of Binder | Type of Gut-Derived Uremic Toxin | Results | |
Phan O. 2005 [79] | apolipoprotein E–deficient mice | 8 weeks of a sevelamer-containing diet | ISI AA | Levels of IS and IAA had not decreased significantly after 8 weeks of a sevelamer-containing diet | |
Clinical Studies | |||||
First Author Year | Type of Study | Patient Type and Numbers | Type of Phosphate Binder | Type of Gut-Derived Uremic Toxin | Results |
Observational Studies | |||||
Guida B. 2013 [80] | Cross-sectional observational study | 57 patients on peritoneal dialysis | Sevelamer (n = 29) Lanthanum (n = 16) No binders (n = 12) | P-cresol | Patients on sevelamer had p-cresol levels significantly lower than those receiving lanthanum or no drug |
Lin C. 2017 [81] | Observational Noncomparative | 5 hemodialysis patients | Sevelamer for 3 months | IS pCS | Significant Reduction in pCS but not IS |
Iguchi A. 2020 [76] | Observational cohort | 18 hemodialysis patients | Sucroferric oxyhydroxide for 3 months | IS pCS | Increase levels of IS and pCS |
Dai L. 2020 [82] | Cross-sectional observational cohort | 423 ESKD patients | Calcium-containing phosphate binders Sevelamer | IS pCS TMAO | Increased levels of IS and TMAO, no change in pCS in sevelamer users vs. sevelamer non-users |
Interventional studies | |||||
Brandenburg V.M. 2010 [83] | Clinical trial (controlled crossover study) | 57 hemodialysis patients | 3-phase trial (A-B-A design; 8 weeks per phase). Sevelamer was only administered in the middle phase of the study. | ISI AA p-cresol | No impact on IS and IAA levels and a significant rise in p-cresol during the sevelamer period |
Riccio E. 2018 [84] | Clinical trial (single-blind, placebo-controlled randomized trial) | 69 CKD patients (grade 3–5, not on dialysis) | Sevelamer vs. placebo for 3 months | p-cresol | Significant Reduction in p-cresol after 3 months of treatment by sevelamer but not placebo |
Bennis Y. 2019 [78] | Clinical trial (multicenter, double-blind, placebo-controlled, randomized) | 78 CKD patients (grade 3–4) | Sevelamer vs. placebo for 3 months | IS pCS IAA | No significant changes in IS, pCS and IAA levels in the sevelamer arm |
Lenglet A. 2019 [85] | Clinical trial (multicenter, open-label, randomized controlled trial) | 100 hemodialysis patients | Sevelamer vs. nicotinamide | IS pCS TMAO | No impact on IS, pCS or TMAO levels in either arm |
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Laville, S.M.; Massy, Z.A.; Kamel, S.; Chillon, J.M.; Choukroun, G.; Liabeuf, S. Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins. Toxins 2021, 13, 91. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020091
Laville SM, Massy ZA, Kamel S, Chillon JM, Choukroun G, Liabeuf S. Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins. Toxins. 2021; 13(2):91. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020091
Chicago/Turabian StyleLaville, Solène M., Ziad A. Massy, Said Kamel, Jean Marc Chillon, Gabriel Choukroun, and Sophie Liabeuf. 2021. "Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins" Toxins 13, no. 2: 91. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020091