The chronic kidney disease of the cat (CKD or CNE)—also called chronic renal insufficiency (CRI or CNI) or chronic renal failure (CRF) in the older literature—is an incurable, progressive disease characterized by a gradual decrease in the nephrons and thus to a decreasing function (insufficiency) of the kidneys. It is one of the most common causes of death in older domestic cats. In current literature, the term "kidney disease" is preferred to the term "renal insufficiency" because the disease initially progresses without any measurable decline in kidney function. Due to the different type of diet and the resulting metabolic peculiarities, the clinical picture and treatment sometimes differ significantly from chronic renal failure in humans.
Chronic kidney disease occurs in cats as a result of inflammation of the renal tubules and the renal interstitial tissue without an identifiable cause (idiopathic tubulointerstitial nephritis). The main symptoms are a reluctance to eat, increased drinking, increased urine output, fatigue, vomiting and weight loss. Chronic kidney disease in cats is divided into four main stages based on the creatinine concentration in the blood plasma, which are further subdivided according to the protein-creatinine quotient in the urine and blood pressure. Treatment is mainly based on reducing the protein and phosphate content of the diet to the basic requirement ("renal diet"). In addition, the numerous secondary symptoms resulting from renal dysfunction, such as disorders of the water, electrolyte and acid-base balance, increased blood pressure, anemia and digestive disorders are treated with medication. If detected and treated early, the progression of the disease can be slowed, the quality of life improved and the life expectancy of the animals increased.
Physiological basics
The kidney is a vital organ with a variety of responsibilities. It plays an important role in maintaining the water, electrolyte and acid-base balance. It excretes toxic metabolic degradation products such as urea. It also recovers valuable substances such as glucose, amino acids, peptides and minerals initially filtered out of the blood during ultrafiltration in the renal corpuscles. In addition, endogenous and exogenous substances are metabolized and broken down in the kidneys—the kidney is therefore a central metabolic organ alongside the liver. Finally, some hormone-active substances are secreted by the kidney, such as renin, erythropoietin and calcitriol (active form of vitamin D3). As a result, the organ plays an important role in the regulation of blood pressure, new blood formation and the balance of calcium and phosphorus, and is thus crucial to bone metabolism, as well.
As carnivores, cats are particularly dependent on the intake of animal proteins because glucose formation from amino acids is their most important energy source. The enzymes of amino acid degradation are adapted to the high protein intake and their activity is largely independent of the protein supply in the diet, so that cats break down endogenous proteins (especially from the muscles) when there is a lack of protein intake (catabolic metabolic state).K. Sturgess: Nutritional management of Renal Disease. In: Proceedings of the 33rd WSAVA/FECAVA Congress, Dublin 2008, p. 281–284.R. Kirby: The cat is not a small dog: In ICU: Parts I and II, Proceedings 29th World Congress oft the WSAVA, Rhodes 2004. Meat and offal also contain vital nutrients for the cat, such as Vitamin A, Taurin or arachidonic acid. Compared to a normal human diet, cats consume around six times as much phosphate in their diet with standard cat food. This makes it difficult to achieve a similar phosphorus reduction in cat food as is aimed at in human medicine for human kidney diets.
Pathophysiological basics
Symptoms of the disease only appear at an advanced stage, when more than two-thirds of the original kidney function has already been lost. This is due to the body's own compensatory mechanisms and the kidney's reserve capacity, which can compensate for the reduced kidney function for a long time and maintain the excretion of urine-requiring substances.D. J. Chew: The role of phosphorus in feline chronic renal disease. In: ESFM Feline Congress 2008 Edinburgh, Scientific Proceedings, p. 59–65.R. Heine: Labordiagnostik bei felinen Nierenerkrankungen. In: Veterinary Focus 18 (2008), p. 16–22. With the loss of functioning nephrons—the functional structural unit of the kidney—the filtering capacity of the renal corpuscles (glomerular filtration rate) decreases and with it the excretory capacity for urinary substances. Acute damage to the tubules can regenerate again if the basement membrane is preserved. However, if a section of the nephron is irreversibly damaged, the entire nephron dies.Karolin Hey: Chronische Nierenerkrankung der Katze – eine tägliche Herausforderung (Teil 1). In: Kleintierpraxis Band 69, No 3, 2024, p. 120–139.
The increased urea levels in the blood (uremia) lead to nausea and vomiting for various reasons. Firstly, they directly irritate chemoreceptors in the chemoreceptor trigger zone in the brain. Secondly, they increase gastrinsecretion and thus lead to an increase in gastric acid production and thus to hyperacidity of the stomach. Finally, they cause vascular inflammation (uraemic vasculitis), which leads to further damage to the digestive tract.Reto Neiger: Chronische Niereninsuffizienz. In: Marian C. Horzinek et al. (Hrsg.): Krankheiten der Katze. Enke, 4. Aufl. 2005, ISBN 3-8304-1049-2, p. 406.Gregory F. Grauer: Chronic renal failure. In: R. W. Nelson und C. G. Couto (Hrsg.): Small animal internal medicine. Mosby, 3. Edition 2003, ISBN 0-323-01724-X, p. 617.
As a result of the accumulation of phosphate in the blood (hyperphosphatemia) and the reduced formation of calcitriol in the remaining main parts, there is a drop in the calcium blood level (hypocalcemia) and increased parathyroid hormone is released from the parathyroid gland. Chronic kidney disease leads to hyperparathyroidism in 84% of cases (secondary renal hyperparathyroidism).Thierry Francey und Elisabeth Müller: Chronische Nierenerkrankung – Früherkennung und Bedeutung der Phosphate. In:veterinary mirror 3 (2010), p. 107–112. Among other things, the parathyroid hormone causes calcium and phosphate to be released from the bones, which ultimately leads to renal bone disorders and calcification of the kidneys, skin, heart and blood vessels. In the kidneys, this calcification contributes to further destruction of the kidney tissue. The reduced responsiveness of the parathyroid cells to calcium disrupts the negative feedback of parathyroid hormone secretion, so that parathyroid hormone continues to be secreted despite the increase in calcium levels. As less phosphate reaches the renal tubules due to the reduced filtration rate, the inhibitory effect of parathyroid hormone on reabsorption in the main body has only a minor effect on the blood phosphate level.
The loss of nephrons and the associated decrease in the number of sodium ion channels leads to a decrease in the concentration gradient in the kidney. However, this is the driving force for water reabsorption in the mid-piece and—in the presence of ADH—also in the collecting ducts. The result is a loss of water via the urine and thus drying out of the body, which is exacerbated by the loss of fluid during vomiting.
One consequence of the kidneys' reduced ability to excrete hydrogen ions, phosphate and sulphate and the excessive loss of bicarbonate is the metabolic acidification of the blood (metabolic acidosis). Metabolic acidosis occurs in 80% of cats with chronic kidney disease.Reto Neiger: Chronische Niereninsuffizienz. In: Marian C. Horzinek et al. (Hrsg.): Krankheiten der Katze. Enke, 4. Edition 2005, p. 410
With increasing kidney damage, the autoregulation of renal blood flow, which normally ensures that the blood flow and thus the filtering capacity up to a threshold of 60 mm Hg are independent of the general blood pressure, is also impaired. As a result, kidney performance is reduced at low blood pressure and, in the case of high blood pressure often associated with chronic kidney disease, further damage occurs due to pressure overload of the renal corpuscles.A. P. Carr, B. Egner: Blood pressure in small animals – Part 2: Hypertension – Target organ damage, heart and kidney. In: Eur. J. Comp. Anim. Pract. 19 (2009), p. 13–17. The increase in blood pressure is due to hardening of the blood vessels in the area of the renal corpuscles, the reduced formation of vasodilating prostaglandins and activation of the renin-angiotensin-aldosterone system.
Occurrence and causes Chronic kidney disease is one of the most common causes of death in older domestic cats.G. F. Grauer: Early detection of renal damage and disease in dogs and cats. In: Vet Clin Small Animal 35 (2005), p. 581–596.A. M. Wolf: Chronic Progressive Renal Disease in the Cat: Recognition and Management In: North American Veterinary Conference Orlando, NAVC Proceedings, Vol. 20, Small Animal Edition, 2006, p. 701–703. In many animals, however, the disease initially remains unrecognized, as clinical symptoms are often absent in the early stages of chronic kidney disease due to the kidney's reserve capacity and sufficiently sensitive diagnostic tests are not available for routine use.A. Parotat, B. Kohn: Die chronische Niereninsuffizienz – Wie sieht ein effektives Management aus? In: kleintier konkret 12 (2009), p. 6–10.R. E. Jepson et al.: Evaluation of predictors of the development of azotemia in cats. In: J. Vet. Intern. Med. 23 (2009), p. 806–813. , PMID 19566846 The data on the frequency of the disease in cats is contradictory, varying between 1.6 and 20%.Thierry Francey, Ariane Schweighauser: Klinische Epidemiologie von Nierenerkrankungen bei der Katze. In: Vet. Focus 28 (2008), p. 2–7. Chronic kidney disease occurs more frequently in older cats: Over 50% of affected cats are seven years old or older and 30% of all cats over 9 years of age show elevated blood levels of nitrogen compounds (azotemia). However, the disease can occur as early as 9 months of age. Disposition predisposition has been proven for Maine Coon, Abyssinian, Siamese, Russian Blue and Burmese.D. J. Polzin et al.: Chronic renal failure. In: S. J. Ettinger und E. C. Feldmann (Hrsg.): Textbook of Veterinary Internal Medicine. Saunders, 5. Edition, Philadelphia 2000, Band 2, p. 1634–1662. ISBN 0-7216-7256-6
Since the kidneys have a high reserve capacity and clinical symptoms only appear when two thirds of the original kidney function has been lost, the triggering factors must damage both kidneys.Sarah Steinbach und Reto Neiger: Chronische Nierenerkrankung: In: Hans Lutz et al. (Hrsg.): Krankheiten der Katze. Enke, 5. Ed. 2014, ISBN 978-3-8304-1243-4, p. 751.
Chronic kidney disease in cats is an idiopathic tubulointerstitial nephritis, i.e. an inflammation of the renal tubules and the renal interstitial tissue without an identifiable cause.Rosanne Jepson: Die Bedeutung von Nierenerkrankungen bei Katzen. In: veterinärspiegel 2013, Heft 2, p. 59–64. In addition to the damage that this primary disease causes directly to the kidney tissue, activated endogenous repair mechanisms such as connective tissue formation lead to further, partially self-sustaining destruction of functional kidney tissue. The reduced ability of the kidneys to excrete sodium and water causes retention (medicine) of these substances and thus an increase in blood volume, which ultimately leads to an increase in blood pressure. About two thirds of all cats with CNE are affected. High blood pressure in turn leads to increased connective tissue formation. A potassium deficiency or excess calcium secondary to other kidney damage also causes further damage to the kidney tissue.