Azotaemia and uraemia in CKD

Cats with chronic kidney disease (CKD) develop azotaemia and, in later stages, uraemia. What exactly are these conditions and how do they differ?


Kidney dysfunction

In the context of chronic kidney disease, azotaemia refers to an increase in the blood levels of the “kidney markers” creatinine and/or urea. There may be an increase in both or only one of the two. Azotaemia shows the dysfunction in relation to the excretory capacity of the kidneys.


Blood marker


Creatinine, which is also used by the international expert group of the International Renal Interest Society (IRIS) as a key marker for diagnosis and staging, is representative of the excretory capacity in the form of glomerular filtration of the kidneys. Creatinine from muscle metabolism is filtered out of the blood by the renal corpuscles (the filtration unit of the nephron, also called the glomerulus). This takes place in the glomerulus and is therefore known as glomerular filtration. If this filtration is inadequate, less creatinine is filtered out of the blood and so builds up in the blood. This causes the blood creatinine level to rise. Increased creatinine indicates impaired excretion.

Creatinine has a very wide normal range. Cats therefore have an individual reference value. Some cats that have a 15-20% increase in their creatinine level, indicating a kidney problem, may still have a creatinine level within the normal range. Having the cat tested annually to know this individual creatinine level is therefore very beneficial. Only then can incipient CKD be detected at an early stage by the above mentioned increase in blood creatinine. Nowadays it is easier to use SDMA. SDMA rises earlier than creatinine when the kidneys are not working as well as they should. Creatinine also depends on the cat’s muscle mass and eating habits: If the muscle mass in CKD is decreasing, for example because the cat is not eating enough (protein), the creatinine level will be lower, giving the impression that the situation is better than it actually is. This is not the case with SDMA as it is independent of muscle mass.



Urea is a waste product of protein metabolism and is also filtered out of the blood via the glomerulus. However, unlike creatinine, it can be reabsorbed from the subsequent tubular system. An increase in urea may initially be related to an increased protein intake. This will result in the production of more urea and an increase in the blood urea level.

If the cat is dehydrated and urine output is therefore reduced, blood urea may be elevated. With high water loss, such as that associated with CKD, the recovery of urea from the tubular system may be reduced, resulting in a lower blood urea level than would be expected for the CKD stage.

Lack of appetite and low protein intake may also reduce urea levels. However, an elevated urea level represents uraemia, especially in the later stages of CKD.

Find out more about the blood tests for CKE here.


Grau getigerte Katze liegt auf der Seite mit den Pfoten in der Luft und schaut in die Kamera
Azotaemia shows the dysfunction in relation to the excretory capacity of the kidneys.

Kidney dysfunction and its clinical consequences

Uraemia is the term used to describe the clinical consequences (symptoms) of reduced kidney function, which includes detoxification and excretion, water and electrolyte regulation, acid-base balance and hormone production. The kidneys also regulate blood pressure (renin hormone), haematopoiesis (erythropoietin hormone) and phosphate and calcium metabolism (calcitriol hormone) through the three hormones they produce. All of these functions are impaired in CKD. This is manifested in a variety of ways, including changes in laboratory values and the appearance of clinical symptoms.


FGF-23: a new player on the field?

FGF-23 has recently been discussed as a laboratory parameter in relation to uraemia. It participates in regulating plasma phosphate levels. Even when phosphate excretion is restricted due to glomerular damage and failure, FGF-23 can keep the phosphate level within the normal range. This parameter may therefore be useful in deciding whether and to what extent phosphate reduction (via diet and/or phosphate binders) is indicated. At present, FGF-23 is not a routine laboratory test when cats are blood tested for renal parameters.

Read more on FGF-23 here.

A villain from within

The situation is different with indoxyl sulphate. This uraemic toxin is a natural product of the microbial breakdown of the amino acid tryptophan. Tryptophan is found in plants and in the meat of herbivorous animals (cattle, sheep, goats, poultry, etc.).

Tryptophan is broken down by the natural intestinal flora in the large intestine. In the process, indole is formed as a precursor. This is transported via the bloodstream to the liver, where it is converted into indoxyl sulphate, the actual uraemic toxin. This uraemic toxin must then be excreted by the kidneys.

10% of the excretion takes place via glomerular filtration and 90% in the tubular system, where it is actively excreted into the urine with the help of a transport system. If both excretion pathways are reduced in CKD, it accumulates in the kidney tissue and causes further damage. This leads to the progression of chronic kidney disease.

In addition, indoxyl sulphate has other adverse effects on the cat’s body: it alters the natural gut flora, causing an imbalance in the bacteria (dysbiosis), resulting in gastrointestinal problems and an additional overproduction of indoxyl sulphate. Indoxyl sulphate is part of the gut-kidney axis, which describes the relationship between changes in the gut microbiota and kidney health, and conversely, the effects of CKD (increased indoxyl sulfate due to inadequate excretion) on the gut microbiota.


Uraemia indicator

In chronic kidney disease (CKD), indoxyl sulphate is involved in many processes that not only cause clinical symptoms (loss of appetite, weight loss, including muscle wasting, vomiting, nausea, diarrhoea) but also promote disease progression. This includes the fact that indoxyl sulphate is known to interfere with phosphate metabolism.

As early as IRIS stage II, higher levels of indoxyl sulphate can be detected in the blood. Indoxyl sulphate levels are highest in stage IV. Efforts to reduce uraemic toxins should be intensified as the level of indoxyl sulphate increases.

Indoxyl sulphate may have prognostic value for the cat’s clinically relevant condition (degree of uraemia). Routine testing is currently only available in one German laboratory.



  • von Luckner, J. & Stieger, N. (2023). Die urämische Katze. In: Katzenmedizin, 13. 24–27.