Examplary Chronic Kidney Disease

Feline chronic kidney disease (CKD) is one of the most common diseases of older cats and the leading cause of death in cats over 5 years of age.

Although its etiology is usually unknown (e.g. toxic causes or viral infections and chronic inflammation), its course is progressive and associated with a variety of clinicopathological changes. This is what makes chronic kidney disease so complex.

There are recommendations for the diagnosis and management of this disease from both the IRIS (= International Renal Interest Society) and the ISFM (International Society of Feline Medicine). In addition, there are newer approaches to detect the disease at an early stage with the help of computer-assisted forecasting techniques to treat cats affected by CKD as early as possible.

For the prognosis of CKD, its severity (= stages of CKD) at the time of initial diagnosis is crucial. This is because early treatment can slow down the progression of the disease and thus increase the cat’s life expectancy. Moreover, the clinical symptoms can be reduced and thus the cat’s quality of life can be improved. Therefore, early detection of CKD is reasonable and recommended by the above-mentioned expert groups. However, in practice, it is often challenging to detect chronic kidney disease at an early stage.

Predicting reduction in filtration capacity

For computerised forecasting as well as for diagnosis and staging= Classification of the cat into a stage of chronic kidney disease according to IRIS... according to IRIS, the 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... blood level is needed.
In feline medicine, creatinine is considered an indicator of the kidneys’ filtration capacity. In human medicine, the so-called glomerular filtration rateThe glomerular filtration rate (GFR) is defined as the volume of fluid that is filtered by the glomeruli of the nephrons of both kidneys per unit of time to produce primary urine. It is, therefore, the chief measure of kidney function. The rate corresponds to... (GFR) is determined. For cats, however, this can only be determined with great effort. The filtration capacity and the creatinine blood level are indirectly proportional to each other: if the kidney capacity decreases, the blood level increases. For the computer modelling, the 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... blood level (also called BUN) as well as the specific gravity of the urine and the age of the cat are also used as predictive variables.

How can you measure the change in filtration efficiency?

Blood urea levels likewise rise when the kidneys’ filtration capacity decreases. Urea is a urinary substance that must be excreted through the kidneys. It has no further significance for the cat’s body. Instead, it is a waste product, such as uraemic toxinsToxic, nitrogen-containing urinary substances responsible for uraemia and kidney damage..... However, urea is not toxic in itself. The urea value is considered an indicator for the amount of retained toxic waste products (= uraemic toxins). These are necessary to be excreted in urine, as well, but are additionally toxic. However, the urea value is dependent on many other factors that are not related to kidney performance. These include the protein content of the feed and the time of the last feed intake.

Similarly the creatinine value is  only a sufficient, but not an absolute indicator of kidney performance, as it depends on muscle metabolism, the muscularity of the cat and also on age, and can vary considerably. The reference range for creatinine is therefore very broad. Thus creatinine is not an accurate absolute indicator for the presence of CKD, but so far it is the best way to diagnose CKD in cats with the help of other factors (e.g. blood urea level, presence of proteinuriaIncreased protein in urine, leading to loss of protein. Normally, only a very small amount of protein is excreted in the urine. In chronic kidney disease, the amount lost may increase. High blood pressure damages blood vessels in the nephrons making them more permeable and..., urine protein-to-creatinine ratio [= UPC], specific urine weight and hypertensionHigh blood pressure.) and to classify it into four stages (IRIS).

The specific gravity of urine is a measure of the kidneys’ ability to excrete dissolved substances (here mainly waste products of metabolism) via water. Because the specific gravity decreases when the kidneys reduce their filtration capacity. In this case, the urine becomes much lighter in colour. Besides a decreased kidney filtration, this can also happen when the cat has consumed a lot of water which must be excreted. The Specific Urine Weight of a single urine sample is therefore difficult to assess.

Invisible start of Chronic kidney disease

For a few years now, there has also been the so-called SDMASDMA = Symmetrical Dimethylarginine, which is a degradation product of the amino acid arginine and is excreted solely through the kidneys. SDMA is a highly specific biomarker for kidney function in cats. Read more: SDMA test (blood test)... test (symmetrical dimethylarginine), which increases even before creatinine when the filtration capacity of the kidneys is reduced. This helps to identify chronic kidney disease in cats up to 17 months earlier.

Likewise, the blood level of the uraemic toxin indoxyl sulfate as a biomarker in cats and dogs with chronic kidney disease could also predict the disease and its progression at an early stage.

With the help of the computer model, which was developed with data from over 100,000 cats, a good prediction of the presence of CKD could be achieved with the above-mentioned four indicators (blood values of creatinine and urea, specific gravity of the urine and age of the cat). Cats with CKD were diagnosed 1-2 years earlier by the model. Especially the interaction of the four indicators is important. The algorithm was able to make good predictions for the four indicators, even or especially when they were still within the normal range, because  changes in the values over time indicated the presence of CKD.

After diagnosis comes staging

By means of the computer model, the current and future risk for CKD is predicted. In contrast, IRIS staging takes place after diagnosis. Organisations such as IRIS and ISFM actively promote long-term monitoring of health status through at least annual check-ups, or even better, bi-annual check-ups for cats over 7 years of age.

In addition to blood and urine tests, the check-ups also include a general examination of the cat with determination of its weight, the so-called body condition score and the cat’s muscular condition. Furthermore, the experts consider blood pressure measurement to be useful, as high blood pressure is often associated with CKD.
The main aim is to detect CKD at an early stage and to be able to treat it accordingly. IRIS staging is applied in order to carry out appropriate treatments. Based on the course of the disease or the corresponding stage.

Chronic kidney disease seldom appears unaided

Lastly inn this large-scale investigation to create the computer model, comorbidities were found, too. I.e. diseases or symptoms that were diagnosed in connection with the CKD. These included hyperthyroidism, diabetes mellitus, inflammatory bowl disease (IBD= Collective term for chronic inflammatory bowel disease of unknown cause, in humans comparable with Crohn's disease....) and symptoms like vomiting, constipation and underweight.  Of which the latter are often associated with CKD but can have other causes, as well.

Bibliography:

• Bradley; R. / Tagkopoulos, I. / Kim, M. / Kokkinos, Y. / Panagiotakos, T. & Elliott, J. (2019): Predicting early risk of chronic kidney disease in cats using routine clinical laboratory tests and machine learning. Journal of Veterinary Internal Medicine, 33, 2644–2656.
• Sparks, A. H. / Caney, S. / Elliot, J. / Finch, N. / Gajanayake, I. / Langston, C./ Lefebvre, H. / White, J. & Quimby, J. (2016): ISFM Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease. Journal of Feline Medicine and Surgery,18, S. 219–239.
• IRIS-Staging: http://www.iris-kidney.com/pdf/IRIS_Staging_of_CKD_modified_2019.pdf