Chronic kidney disease in cats (CKD) is not only associated with health impairments, but often with central nervous symptoms as well. The involvement of the brain as a cause is not fully investigated. Two new studies, carried out on rats and mice respectively, now see a connection between the accumulation of uraemic toxinsToxic, nitrogen-containing urinary substances responsible for uraemia and kidney damage.... in the brain and its influence on well-being. First and foremost is the most potent kidney toxin: indoxyl sulphate. This accumulates in the brain and leads to an impairment of cognitive functions. These include memory and motor coordination for example. It can also lead to symptoms such as apathetic behaviour, confusion and disorientation. Behavioural changes have also been described in this context.
The accumulation of indoxyl sulphate in the brain is held responsible for a variety of pathological brain changes (= encephalopathy). Indoxyl sulphate is thus not only a potent kidney poison, but also presents itself as a brain toxin.
From potent kidney poison to brain toxin
Indoxyl sulphate is already known as part of the gut-kidney axis. The gut-kidney axis describes the connection between uraemic toxins naturally produced in the gut and their negative effects on the integrity of the kidneys.
Indoxyl sulphate is formed from tryptophan. Tryptophan, in turn, is an essential amino acid found in all common meats and internal organs. These include, for example, beef, chicken, pork, etc. Since cats, as obligate carnivores, consume a lot of high-quality protein (muscle meat & organs), it is difficult to feed cats without this essential amino acid. Tryptophan as an essential amino acid must be included in every feed. It is considered essential because mammals form serotonin from tryptophan. Serotonin, a messenger substance (= neurotransmitter), is indispensable for the function of the brain. Serotonin is also known as a mood enhancer. However, the output of serotonin from tryptophan is very low (less than 5%), which means that many degradation products are produced. The body excretes these via the kidneys.
When tryptophan is broken down in the intestine, one breakdown product in particular is produced to a large extent: indole, which is the pre-stage of indoxyl sulphate. Indole is transported to the liver via the bloodstream. Only in the liver does the actual uraemic toxin indoxyl sulphate develop from the pre-stage indole.
As a toxic degradation product, indoxyl sulphate must also be excreted through the kidneys.
Damage is pre-programmed
If it is not filtered out sufficiently by the kidneys, indoxyl sulphate accumulates in many organs and also in the muscles and can cause considerable damage there. Through various stages, indoxyl sulphate leads to inflammation in vessels and tissues and thus to tissue destruction and impairment. Thus, indoxyl sulphate is also involved in the progression of CKD: first, it accumulates in the serum and then in the kidneys, where it destroys the nephronsNephrone sind die Filtereinheiten der Nieren..... This reduces kidney output and even less indoxyl sulphate can be excreted. Consequently, the blood level of indoxyl sulphate increases and subsequently the tissue level in organs such as the brain, where it then causes damage and thus impairment.
I have covered this in detail in my blog article Uraemic Toxins.
Reversion of cognitive impairment through reduction of indoxyl sulphate
The studies mentioned earlier show that indoxyl sulphate, when it accumulates in the brain, can lead to cognitive problems therein. These include the learning and memory defects described above.
On the positive side, the use of an orally administered carbon adsorber reversed the cognitive dysfunctions in the mice studied. The adsorber from human medicine, whose mode of operation is based on binding the pre-stage indole in the intestine, led to a reduction of the indoxyl sulphate level and thus to a reduced tissue level in the brain.
The product consists of carbon spheres of very small size. On the surface of these spheres there are tiny apertures through which only the smallest substances such as indole can pass. Especially as these are fixed in the core of the carbon sphere by charges, so that they are excreted with the spheres via the faeces. Small molecules that fit through the apertures but do not have the appropriate charge are thus not bound, which results in the selectivity of the carbon spheres.
This principle has been proven in human medicine in a large number of studies to successfully reduce indoxyl sulphate in patients with chronic kidney disease. As a result, both the life expectancy and the quality of life of CKD patients could be increased through a reduction of clinical symptoms.
Carbon adsorbers as an outlook for cats
Since 2018, there is now also a product for cats with the same mode of operation. The carbon-based product (active ingredient Renaltec®), which also consists of tiny carbon spheres, takes care of the preliminary stages of uraemic toxins. There is also an advantage over the human product: the selective adsorber developed for cats has an improved capacity to adsorb indole, which makes it even more efficient.
Furthermore, these special products should not be confused with medicinal or activated charcoal. The latter is not specific for the preliminary stages of uraemic toxins.
Bibliography:
- Karbowska, M.; Hermanowicz J. M.; Tankiewicz-Kwedlo, A.; Kalaska, B.; Kaminski, T. W.; Nosek, K.; Wisniewska, R. J. & Pawlak, D. (2020): Neurobehavioral effects of uremic toxin–indoxyl sulfate in the rat model. Nature – Scientific Reports, 10:9483.
- Li, L.-C. ; Chen, W.-Y.; Chen J.-B.; Lee, W.-C.; Chang, C.-C.; Tzeng, H.-T.; Huang, C.-C.; Chang, Y.-J. und Yang, J.-L. (2021): The AST-120 Recovers Uremic Toxin-Induced Cognitive Deficit via NLRP3 Inflammasome Pathway in Astrocytes and Microglia. Biomedicines, 9, 1252, S. 1–18.
