Blood tests

Blood tests for the diagnosis of CKD

Blood serum tests for creatinine and urea are particularly important for diagnosis. In chronic kidney disease (CKD), both levels are elevated (azotemia = increased levels of nitrogenous breakdown products of protein metabolism in the blood).

Blood tests for creatinine and urea or SDMA alone are not sufficient to diagnose CKD. Further tests must be performed according to the IRIS guidelines to rule out CKD or to confirm the diagnosis.

Creatinine

Creatinine is a breakdown product of muscle metabolism and is excreted in the urine. Creatinine itself is an indicator of the kidney’s filtration capacity, as it can only be excreted by the kidneys. However, there are a number of factors that can affect blood creatinine levels. These include periods of hunger, fluid intake, muscularity, nutritional status of the cat, etc. This is a problem in lean and emaciated cats, where the creatinine level may be too low for these reasons.

Each cat therefore has its own reference value. The reference value (= normal value) for creatinine in cats is relatively wide, ranging from 40-170 µmol/litre. It is therefore a good idea to have a blood test for creatinine in healthy cats every year to know their individual creatinine level. This is important because an increase within the reference range, in conjunction with specific urine tests and the SDMA test, can indicate the presence of CKD. The International Renal Interest Society (IRIS) considers creatinine to be the main criterion for diagnosis and staging.

Creatinine blood value rises within reference interval

SDMA-Test

SDMA = Symmetric dimethylarginine, which is a breakdown product of the amino acid arginine and is excreted exclusively by the kidneys. SDMA is a highly specific biomarker of renal function in cats. According to the test manufacturer IDEXX, it can be used to identify cats with CKD at an early stage, when 60% of the nephrons are still functional and there is no increase in creatinine or clinical symptoms.

SDMA has the advantage over creatinine in that it is not influenced by other factors such as muscle mass, etc. and increases at a very early stage of CKD because it correlates very directly with a reduction in filtration capacity (the so-called glomerular filtration rate = GFR).

A study by HALL et al (2014) showed that the SDMA test was able to diagnose CKD on average 17 months earlier than creatinine blood tests.

The SDMA test can be used to detect CKD at an early stage.

An SDMA level > 14 µg/dl indicates CKD.

Early detection of CKD can lead to better and more targeted treatment, with the possibility of prolonging the cat’s life and improving its quality of life.

Therefore, cats should have their kidneys checked once a year from the age of 7.

Urea

Blood Urea is also abbreviated as BUN. Urea is a nitrogenous breakdown product of protein metabolism that must be excreted in the urine. Urea itself is not a toxin, but is used as an indicator of toxic breakdown products of protein metabolism (“uraemic toxins”), which are more difficult to measure. When the kidneys are unable to filter urea adequately, it accumulates in the blood. This is expected in CKD. However, the blood urea level also depends on other factors (the cat’s nutritional status, dehydration, high blood pressure, gastrointestinal bleeding, diabetes, kidney stones, etc.). Therefore, an elevated BUN alone is not a clear indication of CKD. The urea level should always be considered in conjunction with the creatinine level. If creatinine is also elevated, this indicates a kidney problem.

An elevated BUN alone may have other causes, such as a high protein meal eaten by the cat. Therefore, the cat must have fasted for approximately 8-12 hours before the urea level is determined. Elevated urea and creatinine levels are also known as azotemia (= elevated levels of urine in the blood). The International Renal Interest Society (IRIS) classifies CKD into four stages based on the presence and severity of azotemia, as measured by the creatinine level. The normal range (= reference range) is 3.5-8.0 mmol/l, BUN is given as 9.8-35.0 mg/dl.

The BUN should be 9.8-35.0 mg/dl.

Phosphate & FGF-23

The level of phosphate in the blood (serum, plasma) gives an indication of whether calcium-phosphate metabolism is disturbed and hormonal derailment (see Phosphate and CKD) has already begun. In most cases, the phosphate level is still within the normal range in the early stages due to hormonal compensation mechanisms (parathyroid hormone and FGF-23 lead to increased excretion of phosphate by the kidneys). However, a phosphate level within the normal range may mask the derailment that leads to disease progression.

Since 2023, it has been possible to measure FGF-23 in the blood. FGF-23 (Fibroblast Growth Factor 23) is a bone hormone whose concentration in the blood increases when calcium-phosphate metabolism is disturbed. Therefore, FGF-23 is the more accurate measure in the early stages of CKD to determine whether a cat will benefit from phosphate reduction. In addition, elevated FGF-23 levels in the early stages are considered to be prognostically unfavourable. However, FGF-23 is also elevated in the presence of elevated blood calcium (=hypercalcaemia), untreated hyperthyroidism and parathyroid hormone or calcitriol alterations unrelated to renal disease, as well as in the presence of inflammation and magnesium deficiency. It is therefore always advisable not to look at individual values but to consider all the parameters of the blood count and other tests.

As diet can influence phosphate and FGF-23 levels, cats must be fasting for the blood test.

The IRIS gives recommendations for maximum phosphate levels at each stage. If these are exceeded, phosphate-reducing measures are recommended. The same applies if the phosphate is within the normal range but the FGF-23 exceeds the threshold of 400 mg/ml.

IRIS recommendations for phosphate reduction in cats with chronic kidney disease

Uraemic Toxins

The uraemic toxin indoxyl sulphate can now be detected in the blood. In some laboratories, this test is already part of the extended kidney profile or can be carried out as an individual test.

The indoxyl sulphate blood level is subject to individual and diurnal fluctuations. And its level is also dependent on the tissue level: Indoxyl sulphate accumulates first into the blood and then back into the organ tissues if it is not excreted sufficiently, as is the case with CKD. There is an exchange between blood and tissue that causes the indoxyl sulphate blood level to vary. This is particularly the case when blood levels are low. In the late IRIS-stages, the indoxyl sulphate level can increase exponentially.

Calcium

Calcium is a mineral that plays an important role in muscle movements (muscle contraction), in blood clotting and also in nerve function. However, most calcium in the body is in the bones. Blood calcium and phosphate levels are linked via various mechanisms (see The hyperphosphataemia vicious circle). CKD can cause both a decrease in blood calcium levels (hypocalcaemia) and an increase (hypercalcaemia). Individual analytic laboratories define normal blood calcium levels differently, and these can differ significantly. In most cases however, the level is 2.3–3.0 mmol/l, although some laboratories consider hypercalcaemia to start at 2.75 mmol/l.

Potassium and sodium

Potassium and sodium are also important nutrient minerals in the body. In CKD, potassium is usually reduced (hypokalaemia) due to frequent urination and vomiting and sodium is usually increased (hypernatraemia).

  • Normal potassium is about 3.0–4.8 mmol/l and normal sodium 145–158 mmol/l.
  • Normal blood calcium should be 2.3–3.0 mmol/l.
  • Normal blood sodium should be 145–158 mmol/l.

Normal blood potassium should be 3.0–4.8 mmol/l.

Erythrocytes and haematocrit

Haematocrit is the volume percentage of red blood cells (erythrocytes) in the stream and is usually lowered in CKD cats. The kidneys are involved in blood formation via the hormone erythropoietin. In CKD, this mechanism is compromised, so fewer red blood cells are produced. This can lead to anaemia, which manifests itself as paleness of the mucous membranes.

In cats the normal erythrocyte count is 5.0–10.0 mio./µl, and the normal haematocrit is 30–45% (0.30–0.45 l/l). Cats are considered to be anaemic at a haematocrit below 27%.

Glomerular filtration rate (GFR)

The glomerular filtration rate is the volume of blood passing through the nephrons  each minute and is therefore the best measure of kidney function. The procedure involves administering the cat a defined amount of a particular marker substance (for example iohexol) that is excreted exclusively, or at least predominantly, via the kidneys. The levels of the substance are then analysed in blood samples collected at specific intervals and in a 24-hour urine sample. The procedure measures how rapidly the kidneys can eliminate the substance (the rate of clearance). As the rate of clearance is directly related to the filtration rate, the GFR can be determined.

Creatinine levels are inversely related to GFR. At a higher glomerular filtration rate the nephrons can clear more creatinine from the blood, and blood creatinine levels drop. At a lower filtration rate less creatinine is cleared and blood creatine rises. Whereas a reduced GFR,  precedes an increase in creatinine; there is a delay between the two changes. GFR measurement is, therefore, well-suited for early detection of CKD. SDMA responds to GFR reduction earlier than creatinine. Hence, the SDMA test is also well-suited to early detection, but is a significantly easier procedure than GFR determination.

Blood tests are important

The blood tests mentioned above are the most important tests for a cat with CKD and are part of its “kidney profile”. In addition, it’s important that a complete blood count is performed to rule out, or to   potential health problems or unrelated disorders. These include, liver and thyroid function tests (the T4 level in particular for the former), diabetes tests based on the fructosamine level and a white blood cell differential test (the percentage of each type of white blood cell, for instance neutrophils, in the blood) to identify potential inflammations.

Depending on the underlying disease, trigger or concomitant disease (for instance secondary hyperparathyroidism), further laboratory tests may be necessary, which your veterinarian will discuss with you.