HPM Cat Feline CKD

Feline chronic kidney disease

Feline chronic kidney disease (CKD) is a condition with a late clinical expression. It results from the progressive reduction in the number of functional nephrons due to irreversible nephropathy, usually bilateral. It is important to detect it as early as possible and to evaluate its stage of evolution according to the classification proposed by the International Renal Interest Society (IRIS).

The different markers of CKD progression

In most mildly uremic cats, urine specific gravity (USG) is less than 1.035, but the decrease in USG is observed later in cats than in dogs. Similarly, proteinuria is classically a marker of early CKD in dogs but is often absent in cats. The presence of hypertension can suggest loss of renal regulatory capacity, but many other abnormalities may be the cause.

In practice, investigation and monitoring of CKD relies primarily on the measurement of parameters such as plasmatic SDMA, creatinine, and urea. Changes in these markers can be correlated with changes in glomerular filtration rate (GFR).

SDMA, an early marker of kidney function

The determination of symmetric dimethylarginine (SDMA) is now routinely available and offers new perspectives in the diagnosis of CKD. Thanks to this early diagnostic tool, it was found that more than 60% of cats over 10 years old suffer from CKD.

SDMA is independent of muscle mass which tends to decrease in older cats.

Several studies have shown a linear relationship between GFR and SDMA concentration in cats over 11 years of age, both azotemic and not. An increase in SDMA above the reference limit corresponds to a decrease of approximately 40% in GFR. In some cases, a decrease of only 25% of GFR is evidenced by an increase in SDMA. On average, this test would allow a diagnosis of CKD to be made 17 months earlier than with creatinine.

FGF23, an early marker of hyperphosphatemia

Mineral and bone disorders (soft tissue and blood vessel calcification, bone demineralisation) are associated with CKD. They are due to hyperphosphataemia and subsequent hyperparathyroidism that develop early in the development of renal disease.

The increase in serum phosphate concentration causes bone secretion of the protein FGF23, which belongs to the family of fibroblast growth factors. This factor has recently been identified : in veterinary medicine, the main interest of measuring FGF23 is that its serum concentration increases in the early stages of CKD, when plasma phosphate concentration is still normal (<4.5 mg/dl or <1.5 mmol/l). Therefore, this assay can be used to identify cats that may benefit from early dietary phosphorus restriction.

Creatinine, a useful tool for monitoring CKD

Creatinine is considered as a good marker of GFR because it is filtered without being reabsorbed or secreted. However, plasma creatinine increases only after a significant loss of functional nephrons, and in early CKD, creatinine varies very little while GFR decreases. This marker therefore lacks sensitivity.

However, monitoring creatinine level is interesting in cats with known CKD, provided that the cat's muscle mass is taken into account; the development of a muscle loss leads to a decrease in creatinine level, but this should not be interpreted as an improvement in GFR.

Plasma urea, not a good marker of GFR

Urea is one of the uremic toxins and its increase can be correlated with clinical manifestations. However, plasma urea is not a good marker of GFR because its production varies according to protein intake, protein catabolism, diuresis, hepatic synthesis, etc. Urea is also influenced by many extra-renal factors, which limit its interest in demonstrating deterioration in renal function.

Follow-up of a cat with CKD

Following diagnosis, ISFM recommends to re-evaluate cats every 1–4 weeks, according to clinical needs. Even in cases of early and apparently stable CKD, initial monthly revisits can be helpful in supporting the diagnosis, providing support to the owner, and in monitoring progression and therapy. In the long term, even if stable, cats should be re-evaluated at least every 3–6 months.

Physical examinations and biological follow-up

At each follow-up visit, a thorough clinical examination will be performed, including weighing, assessment of body score, muscle mass and hydration. In addition to renal markers, phosphatemia (which increases in conjunction with GFR markers) and calcium (hypercalcemia is present in 10-30% of cats with CKD) should be monitored.
Given the multiple metabolic roles of the kidney, renal dysfunction is likely to result in numerous electrolytes, acid-base, and hematologic disturbances. An ionogram, hematocrit, and urinalysis (USP and dipstick) are therefore also part of the complementary tests to be performed.

Nutritional adaptations

Limiting dietary phosphorus

In stages 1 and 2, non-azotemic cats with normal serum phosphate levels are likely to benefit from a phosphorus-reduced diet if their serum FGF23 level is elevated. In the absence of hypercalcemia, anemia, or marked inflammatory disease, progressive restriction of dietary phosphate is indicated if the serum FGF23 level is >400 pg/ml. The plasma phosphate concentration should remain between 2.7 mg/dl and 4.5 mg/dl (or 0.9 mmol/l to 1.5 mmol/l 5. In stage 3, it is more realistic to aim for a plasma phosphate concentration <5.0 mg/dl or <1.6 mmol/l.

If plasma phosphate concentration remains excessive despite dietary restriction, a phosphate binder will be administered with each meal (such as aluminum hydroxide, aluminum carbonate, calcium carbonate, calcium acetate, lanthanum carbonate). Serum calcium and phosphate levels will be monitored every 4-6 weeks until the concentrations are stable, and then every 12 weeks.

Dietary protein restriction

Iris recommends switching cats to a kidney-targeted diet as early as stage 2 of CKD because it is easier to make this dietary transition early in the course of the disease, before inappetence develops in the cat. In addition, in stage 2, it is helpful to minimize the amount of waste products from protein metabolism by limiting protein intake. Protein restriction will progressively increase as azotemia progresses (stages 3 and 4). The quality of the protein provided should compensate for the decrease in quantity, to avoid any deficit in essential amino acids.

Controlling phosphorus and protein intake slows disease progression and improves survival in CKD cats.

In cats, CKD usually evolves over several years. Complications may arise during the course of the disease, leading to a sudden deterioration in renal function and the appearance of signs of a uremic crisis.

Sources

SPARKES A.H., “ISFM Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease”, J. Feline Med. Surg., 2016, 18(3), 219–39.
MARINO C.L., et al., « Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies », J. Fel. Med. Surg., 2014, 16, 465-472.
YERRAMILLI M., et al., “Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics”, Vol. 46, Veterinary Clinics of North America - Small Animal Practice. W.B. Saunders; 2016. p. 961–93.
SARGENT H.J. et al, « Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats”, J. Vet. Intern. Med., 2019, 33(6), 2657–64.
INTERNATIONAL RENAL INTEREST SOCIETY (IRIS), “Treatment recommendations for CKD in cats”, 2023, www.iris-kidney.com/pdf/IRIS_CAT_Treatment_Recommendations_2023.pdf

Osteoarthritis in the older cat

Osteoarthritis is characterized by the deterioration of articular cartilage and the presence of bone neoformations on the surface and periphery of affected joints. In cats, the most commonly affected joints are hips and elbows, but spinal lesions are also common, generally between the 7th and 10th thoracic vertebrae, and more severely in the lumbar and lumbosacral regions.