KIDNEY-HEART AXIS – WHEN THE HEART BEATS ON THE KIDNEYS AND VICE VERSA

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Kidney-heart axis – when the heart beats on the kidneys and vice versa

Uraemic toxinsToxic, nitrogen-containing urinary substances responsible for uraemia and kidney damage.... are involved in numerous processes in the body. They are closely related to the gut-kidney axis, and the more I delve into the subject, the clearer this becomes to me.
But other organs also play an important role in this relationship. A new paper on the subject has recently been published. For the first , it deals with the topic of kidney dysfunction, uraemic toxins (in particular indoxyl sulphate) and their effect on the heart and blood vessels of dogs.

The paper describes a human medical study from Japan, which was conducted on dogs. As part of the study, cardiac dysfunction was artificially induced in dogs. Animal experimentationBasic research is unfortunately still often conducted on animals, such as dogs, particularly in human medicine. The findings from such research can frequently be applied to other animals, such as humans or cats.... is a disturbing the benefits it brings are clear. Similarities in the physiology of animals mean that the findings of this study are relevant both to human and to veterinary medicine. Up until now, there has been no veterinary research on this topic. This study, therefore, can also provide evidence on how the disease progresses in cats and its association with the heart-kidney axis.

Two against one – the kidneys make it difficult for the heart

Chronic heart disorders are particularly linked to chronic kidney disease and vice versa. The physiology of both organs is intimately connected, amongst other things due :

• the renin-angiotensin-aldosterone system (RAAS),
• phosphate and calcium blood levels,
• anaemia,
• oxidative stress, and
• inflammatory reactions.

The uraemic toxin indoxyl sulphate has an effect on all these. The higher its level in the blood, the more the systems are affected and the higher the level of phosphate in the blood, resulting in inflammation in various organs, especially in the kidneys and heart.

This was the rationale for further investigating indoxyl sulphate levels as an important biomarker for cardiac dysfunction progression.

Similar studies have been conducted on the relationship between indoxyl sulphate levels and chronic kidney disease progression, a relationship that has been demonstrated several times and is currently being studied in dogs and cats. (see uraemic toxins)

Once again, indoxyl sulphate

Indoxyl sulphate is associated with more pathological effects than any other uraemic toxin, followed by para-cresyl sulphate. Both have their origin in the microbial breakdown of food proteins in the intestines (see The intestines aren’t just charming). In doing so, intestinal microbes break down crucial amino acids such as tryptophan, tyrosine and, respectively, phenylalanine to form the toxin precursors indole and para-cresol. Both precursors then enter the bloodstream via the intestines and are transported to the liver, where they are converted into the actual uraemic toxins, indoxyl sulphate and para-cresyl sulphate. The liver releases the uraemic toxins into the blood, from which they are filtered out in the kidneys to be excreted with the urine. In chronic kidney disease, the kidneys can no longer sufficiently filter out the excessive amount of these uraemic toxins and other breakdown products. “Waste” builds up in the blood and the blood levels of the uraemic toxins indoxyl sulphate and para-cresyl sulphate rise. This opens the door on their toxic effects in the body (see uraemic toxins).

The Japanese study

In the above-mentioned study by a Japanese research group led by Hiroshi Asanuma (2019), twelve dogs in total were artificially induced to develop a heart defect. The dogs were then divided into two groups. One group received a uraemic toxin binder called AST-120, while the other received no treatment.

Dogs in the untreated group showed an increase in indoxyl sulphate blood levels and, in parallel, a deterioration in heart function. In contrast, in the treated group, indoxyl sulphate blood levels dropped to the baseline values.

These results are thought to be transferable to people with heart dilatation. The reduction in indoxyl sulphate in the body reduced hypertrophyHypertrophy (an increase in cell size) and hyperplasia (an increase in cell number) lead to an increase in the size of tissues and organs. Atrophy is the direct opposite of both hypertrophy and hyperplasia...., fibrosis and inflammation of the heart tissue.

Such pathologies involve many mediators in the heart, such as FSG-23, the renin-angiotensin-aldosterone system (RAAS) and erythropoietinErythropoietin, abbreviated to EPO, is a growth factor that stimulates red blood cell production. EPO can be produced biotechnologically and administered for kidney failure or after chemotherapy..... Indoxyl sulphate has a negative effect on all these.

This study demonstrated that AST-120 effectively reduced the levels of indoxyl sulphate and prevented the progression and worsening of heart failure in dogs.

AST-120 & Renaltec®: The secret of the black spheres.

AST-120 is a carbon-based adsorber in spherical form intended to bind intestinal precursors of uraemic toxins. It has been administered for many years in Asian countries to people with chronic kidney disease to lower indoxyl sulphate levels. The reduction in indoxyl sulphate increases survival rate and delays the need for patients to start dialysis. In addition, the reduction in indoxyl sulphate also improves patients’ symptoms. These are usually associated with uraemiaA raised level in the blood of urea and other urinary substances, which in chronic kidney disease can no longer be adequately excreted due to impaired renal function (glomerular filtration rate). This leads to renal damage due to uraemic toxins, toxic urinary substances The symptoms.... AST-120 binds the uraemic precursors in the gut, independent of the kidneys. The result is that these bound precursors can then no longer produce uraemic toxins (see The intestines aren’t just charming).

AST-120 consists of tiny spherical carbon particles that are ingested and roll through the gastrointestinal tract while adsorbing the uraemic toxin precursors in the intestines. They are passed out with the faeces after they are “filled”. AST-120 is on the market in Japan for chronic kidney disease in cats, where it has also been successfully employed in humans. It is not on the market, however, in Europe and America, either for humans or animals.

Nevertheless, since last year an “improved” AST-120 for cats has been available in some parts of Europe, which contains the ingredient Renaltec®. This is also made of pure carbon and consists of tiny spherical particles. Renaltec® is therefore, in principle, very similar to AST-120.

Recent studies have, however, demonstrated that Renaltec® binds significantly more indole than AST-120, possibly due to its even greater selectivity. Its effect is correspondingly stronger, as its ability to reduce indoxyl sulphate in the blood is likewise more pronounced. Its selectivity – its capacity for binding particular molecules within its spheres – allow it to bind more harmful (and less beneficial) substances (see blog article “The intestines aren’t just charming”). This prevents nutritional deficiencies. The higher the selectivity, the better.
Activated charcoal, which is used to treat diarrhoea or acute poisoning, for example, is not very smooth spherical particles, which protect the mucous membrane, but of splinters and sharp needles. These irritate the mucous membrane in the gastrointestinal tract in the long term and can lead to constipation and abdominal pain. It should, therefore, only be taken for a short time.

Discussion of the results of the Japanese study

The Japanese research group was able to prove a connection between the intestines, liver, kidney and heart. The study demonstrated that in dogs with artificially induced cardiac failure, indoxyl sulphate blood levels increased. However, this was reduced by treatment with AST-120.

The control of indoxyl sulphate levels by AST-120 study in dogs with induced heart failure (or alternatively by Renaltec® in Europe) found by the Japanese is likely to find its way into clinical practice to treat dogs with heart disease.

Renaltec®, which has already been proven to reduce indoxyl sulphate in cats, should be even more effective in reducing indoxyl sulphate than it can also adsorb more indole.

Renaltec® is the first selective high-performance adsorber available in Europe for breaking the gut-kidney axis in veterinary medicine (cats). By lowering the level of indoxyl sulphate, it provides a new and gentle approach not only for cats with chronic kidney disease, but also, interestingly, for breaking the renal-heart axis.

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Bibliography:

• Asanuma et al. (2019): AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs, Cardiovascular Drugs and Therapy, 23 March 2019