The uraemic toxin vicious cycle
A decline in the performance of the kidneys initiates a vicious cycle. As nephronsNephrone sind die Filtereinheiten der Nieren.... are progressively lost and renal insufficiency worsens, ever fewer urinary substances such as creatinineCreatinine is a breakdown product of muscle metabolism. Its blood level is dependent, among many factors, on age, weight, nutritional status and muscle mass. Hence, creatinine levels in the blood vary from individual to individual. Creatinine is continuously excreted in the urine. Increased blood creatinine... and ureaUrea is the nitrogen-containing breakdown product of protein metabolism. The nitrogen from the proteins is converted to ammonia in the liver, which is combined with carbon dioxide to form urea. This is continuously excreted via the kidneys but also via sweat. Urea is one of... are filtered out and excreted. Neither of these are uraemic toxinsToxic, nitrogen-containing urinary substances responsible for uraemia and kidney damage...., but their levels are measured to diagnose progression of the disease (→ see Diagnostics and Stages). Renal insufficiency leads to an accumulation of nitrogen-containing urinary substances in the blood (azotaemiaIncreased levels of nitrogen-containing breakdown products of protein metabolism in the blood....).
Elevated blood levels of such urinary substances indicate an azotaemia. Creatinine and urea serve as indicators of kidney performance and are tested in the blood. Chronic kidney disease (CKD) is diagnosed and classified into four stages on the basis of the plasma levels of these substances.
Uraemic toxins need to be excreted in the urine. They are toxic substances from the natural processes of protein metabolism and are usually excreted via the kidneys. If their level rises in the blood due to reduced kidney filtration capacity, they can accumulate in the blood and directly damage the kidneys. Uraemic toxins include indoxyl sulfate and para-cresyl sulfate. These are very harmful to the kidneys. Extensive studies in humans and rats have shown that indoxyl sulfate is directly linked to mortality in chronic kidney disease. Indoxyl sulfate causes destruction of cells, leading to inflammation. The result is a destruction of nephrons and their replacement by scar tissue, continuing the cycle of reduced renal performance and further nephron destruction. In addition, uraemic toxins can have an adverse effect on bone metabolism.
Ongoing accumulation of uraemic substances in the blood, also known as 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..., is toxic for the body. This is associated with clinical symptoms, such as vomiting, nausea, lethargy, diarrhoea, weakness, bad breath, shaggy coat – and even comatose states. Being able to control urinary substances and especially uraemic toxins is very important, as it is not feasible to provide the equipment for dialysis (blood cleansing) of cats.

This vicious cycle can be influenced, as the level of uraemic toxins is directly related to the amount of protein in the diet and protein digestion in the gut. In human medicine, patients can be treated with an approach that prevents uraemic toxin precursors from being taken up into the body from the intestine. This can reduce the burden on the kidneys, since fewer uraemic toxins are produced. You can find out more about this on Treatment.